A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)
Compounds with a core of fused benzo-pyran rings.
Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.
Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.
An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)
A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)
Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.
A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.
A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
Drugs used to cause dilation of the blood vessels.
A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)
That phase of a muscle twitch during which a muscle returns to a resting position.
A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.
A 37-amino acid residue peptide isolated from the scorpion Leiurus quinquestriatus hebraeus. It is a neurotoxin that inhibits calcium activated potassium channels.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
10-carbon saturated monocarboxylic acids.
Organic compounds containing both the hydroxyl and carboxyl radicals.
The nonstriated involuntary muscle tissue of blood vessels.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.
Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed)
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system.
One of a pair of thick-walled tubes that transports urine from the KIDNEY PELVIS to the URINARY BLADDER.
A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.

Acetylcholine-induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice. (1/374)

1. Isometric tension was recorded in isolated rings of aorta, carotid, coronary and mesenteric arteries taken from endothelial nitric oxide synthase knockout mice (eNOS(-/-) mice) and the corresponding wild-type strain (eNOS(+/+) mice). The membrane potential of smooth muscle cells was measured in coronary arteries with intracellular microelectrodes. 2. In the isolated aorta, carotid and coronary arteries from the eNOS(+/+) mice, acetylcholine induced an endothelium-dependent relaxation which was inhibited by N(omega)-L-nitro-arginine. In contrast, in the mesenteric arteries, the inhibition of the cholinergic relaxation required the combination of N(omega)-L-nitro-arginine and indomethacin. 3. The isolated aorta, carotid and coronary arteries from the eNOS(-/-) mice did not relax in response to acetylcholine. However, acetylcholine produced an indomethacin-sensitive relaxation in the mesenteric artery from eNOS(-/-) mice. 4. The resting membrane potential of smooth muscle cells from isolated coronary arteries was significantly less negative in the eNOS(-/-) mice (-64.8 +/- 1.8 mV, n = 20 and -58.4 +/- 1.9 mV, n = 17, for eNOS(+/+) and eNOS(-/-) mice, respectively). In both strains, acetylcholine, bradykinin and substance P did not induce endothelium-dependent hyperpolarizations whereas cromakalim consistently produced hyperpolarizations (- 7.9 +/- 1.1 mV, n = 8 and -13.8 +/- 2.6 mV, n = 4, for eNOS(+/+) and eNOS(-/-) mice, respectively). 5. These findings demonstrate that in the blood vessels studied: (1) in the eNOS(+/+) mice, the endothelium-dependent relaxations to acetylcholine involve either NO or the combination of NO plus a product of cyclo-oxygenase but not EDHF; (2) in the eNOS(-/-) mice, NO-dependent responses and EDHF-like responses were not observed. In the mesenteric arteries acetylcholine releases a cyclo-oxygenase derivative.  (+info)

Differential effects of pinacidil, cromakalim, and NS 1619 on electrically evoked contractions in rat vas deferens. (2/374)

AIM: To compare the inhibitory action of electrically evoked contractions of rat epididymal vas deferens by pinacidil (Pin), cromakalim (Cro), and NS 1619. METHODS: Monophasic contractions were evoked by electric field stimulation in rat isolated epididymal half of vas deferens. RESULTS: Newly developed ATP-sensitive K+ channel openers, Pin and Cro, concentration-dependently reduced the electrically evoked (0.3 Hz, 1 ms pulse duration, 60 V) contractions and glibenclamide but not charybdotoxin antagonized the inhibitory effects of both agents. Pin shifted the concentration-response curve for norepinephrine to the right with reducing the magnitude of the maximum contraction in a glibenclamide-sensitive fashion. The large-conductance Ca(2+)-activated K+ channel opener, NS 1619, inhibited the electrically evoked contractions in a concentration-dependent manner. Charybdotoxin (100 nmol.L-1) partially reduced the effect of NS 1619 but glibenclamide (10 mumol.L-1) showed no effect. None of these 3 agents affected the basal tension. CONCLUSION: Both ATP-sensitive and Ca(2+)-activated K+ channels presented in vas deferens smooth muscles involved in regulation of muscle contractility.  (+info)

Role of K+ channels in A2A adenosine receptor-mediated dilation of the pressurized renal arcuate artery. (3/374)

1. Adenosine A2A receptor-mediated renal vasodilation was investigated by measuring the lumenal diameter of pressurized renal arcuate arteries isolated from the rabbit. 2. The selective A2A receptor agonist CGS21680 dilated the arteries with an EC50 of 130 nM. The CGS21680-induced vasodilation was, on average, 34% less in endothelium-denuded arteries. 3. The maximum response and the EC50 for CGS21680-induced vasodilation in endothelium-intact arteries were not significantly affected by incubation with the K+ channel blockers apamin (100 nM), iberiotoxin (100 nM), 3,4-diaminopyridine (1 mM), glibenclamide (1 microM) or Ba2+ (10 microM). However, a cocktail mixture of these blockers did significantly inhibit the maximum response by almost 40%, and 1 mM Ba2+ alone or 1 mM Ba2+ in addition to the cocktail inhibited the maximum CGS21680-response by 58% and about 75% respectively. 4. CGS21680-induced vasodilation was strongly inhibited when the extracellular K+ level was raised to 20 mM even though the dilator response to 1 microM levcromakalim, a K(ATP) channel opener drug, was unaffected. 5. CGS21680-induced vasodilation was inhibited by 10 microM ouabain, an inhibitor of Na+/K(+)-ATPase, but ouabain had a similar inhibitory effect on vasodilation induced by 30 nM nicardipine (a dihydropyridine Ca2+ antagonist) or 1 microM levcromakalim. 6. The data suggest that K+ channel activation does play a role in A(2A) receptor-mediated renal vasodilation. The inhibitory effect of raised extracellular K+ levels on the A(2A) response may be due to K(+)-induced stimulation of Na+/K(+)-ATPase.  (+info)

ATP-sensitive potassium channels regulate in vivo dopamine release in rat striatum. (4/374)

ATP-sensitive K+ channels (K(ATP)) are distributed in a variety of tissues including smooth muscle, cardiac and skeletal muscle, pancreatic beta-cells and neurons. Since K(ATP) channels are present in the nigrostriatal dopamine (DA) pathway, the effect of potassium-channel modulators on the release of DA in the striatum of conscious, freely-moving rats was investigated. The extracellular concentration of DA was significantly decreased by the K(ATP)-channel opener (-)-cromakalim but not by diazoxide. (-)-Cromakalim was effective at 100 and 1000 microM concentrations, and the maximum decrease was 54% below baseline. d-Amphetamine significantly increased extracellular DA levels at the doses of 0.75 and 1.5 mg/kg, s.c. with a 770% maximum increase. (-)-Cromakalim had no effect on d-amphetamine-induced DA release, while glyburide, a K(ATP) blocker, significantly potentiated the effects of a low dose of d-amphetamine. These data indicate that K+ channels present in the nigrostriatal dopaminergic terminals modulate basal release as well as evoked release of DA.  (+info)

Thiopental and propofol impair relaxation produced by ATP-sensitive potassium channel openers in the rat aorta. (5/374)

ATP-sensitive potassium channel openers are used as vasodilators in the treatment of cardiovascular disorders. The effects of i.v. anaesthetics on arterial relaxation induced by ATP-sensitive potassium channel openers have not been studied. Therefore, in this study, we have examined if thiopental (thiopentone) and propofol affect the vascular response to the ATP-sensitive potassium channel openers, cromakalim and pinacidil, in the isolated rat aorta. Rings of rat thoracic aortas without endothelium were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative manner. During submaximal contractions with phenylephrine 0.3 mumol litre-1, relaxation after cromakalim 0.1-30 mumol litre-1, pinacidil 0.1-30 mumol litre-1 and papaverine 0.1-300 mumol litre-1 was demonstrated. Thiopental 30-300 mumol litre-1, propofol 10-100 mumol litre-1, 10% Intralipid 45 microliters or glibenclamide 5 mumol litre-1 were applied 15 min before addition of phenylephrine. During contractions with phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxation. A selective ATP-sensitive potassium channel antagonist, glibenclamide 5 mumol litre-1, abolished this relaxation, whereas it did not affect relaxation produced by papaverine. Thiopental concentrations > 30 mumol litre-1 significantly impaired relaxation produced by cromakalim or pinacidil. Propofol concentrations > 10 mumol litre-1 also significantly reduced relaxation produced by cromakalim or pinacidil, whereas Intralipid was ineffective. Thiopental 300 mumol litre-1 and propofol 100 mumol litre-1 did not alter relaxation produced by papaverine. These results suggest that the i.v. anaesthetics, thiopental and propofol, impaired vasodilatation mediated by ATP-sensitive potassium channels in vascular smooth muscle cells.  (+info)

Effects of nicorandil as compared to mixtures of sodium nitroprusside and levcromakalim in isolated rat aorta. (6/374)

1. The contribution of the relaxant mechanisms of nicorandil (NIC) were analysed by comparing its effects with those of sodium nitroprusside (SNP), levcromakalim (LEM) and mixtures (1:10, 1:30 and 1:100) of SNP:LEM in isolated endothelium-denuded rat aorta. 2. In rings precontracted with KCl (25 mM), the relative inhibitory potency of the soluble guanylate cyclase inhibitor ODQ and the K(ATP) channel inhibitor glibenclamide (GLI) on SNP:LEM mixtures showed a good correlation with the relative proportion of SNP and LEM in the mixtures. Furthermore, the degree of the inhibition by ODQ and GLI of the effects of the 1:30 SNP:LEM mixture varied as a function of the relative potency of SNP and LEM in KCl-, noradrenaline- (NA) or NA plus nifedipine-treated arteries. 3. The inhibitory effects of ODQ, GLI and ODQ plus GLI on NIC-induced relaxation was similar to that for the 1:30 SNP:LEM mixture in NA plus nifedipine-contracted arteries, but the inhibition of GLI or ODQ plus GLI was smaller in KCl-contracted arteries. 4. In conclusion, the relative importance of activation of the cyclic GMP pathway and K(ATP) channel opening in mixtures of SNP and LEM could be predicted by the proportion of the drugs in the mixtures and by the relative potency of SNP vs LEM in different experimental conditions. Furthermore, the present results suggest that besides these two mechanisms, a third ODQ- and GLI-insensitive mechanism, possibly involving Ca2+ channel blockade, also participates in the relaxant effects of NIC in KCl-induced contractions.  (+info)

Differential effects of lidocaine and mexiletine on relaxations to ATP-sensitive K+ channel openers in rat aortas. (7/374)

BACKGROUND: In cardiac myocytes, lidocaine reduces but mexiletine increases adenosine triphosphate (ATP)-sensitive K+ currents, suggesting that these class Ib antiarrhythmic drugs may differentially modify the activity of ATP-sensitive K+ channels. The effects of lidocaine and mexiletine on arterial relaxations induced by K+ channel openers have not been studied. Therefore, the current study was designed to evaluate whether lidocaine and mexiletine may produce changes in relaxations to the ATP-sensitive K+ channel openers cromakalim and pinacidil in isolated rat thoracic aortas. METHODS: Rings of rat thoracic aortas without endothelia were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative fashion. During submaximal contractions to phenylephrine (3 x 10(-7) M), relaxations to cromakalim (10(-7) to 3 x 10(-5) M), pinacidil (10(-7) to 3 x 10(-5) M), or diltiazem (10(-7) to 3 x 10(-4) M) were obtained. Lidocaine (10(-5) to 3 x 10(-4) M), mexiletine (10(-5) to 10(-4) M) or glibenclamide (5 x 10(-6) M) was applied 15 min before addition of phenylephrine. RESULTS: During contractions to phenylephrine, cromakalim and pinacidil induced concentration-dependent relaxations. A selective ATP-sensitive K+ channel antagonist, glibenclamide (5 x 10(-6) M), abolished these relaxations, whereas it did not alter relaxations to a voltage-dependent Ca2+ channel inhibitor, diltiazem (10(-7) to 3 x 10(-4) M). Lidocaine (more than 10(-5) M) significantly reduced relaxations to cromakalim or pinacidil in a concentration-dependent fashion, whereas lidocaine (3 x 10(-4) M) did not affect relaxations to diltiazem. In contrast, mexiletine (more than 10(-5) M) significantly augmented relaxations to cromakalim or pinacidil. Glibenclamide (5 x 10(-6) M) abolished relaxations to cromakalim or pinacidil in arteries treated with mexiletine (10(-4) M). CONCLUSIONS: These results suggest that lidocaine impairs but mexiletine augments vasodilation mediated by ATP-sensitive K+ channels in smooth muscle cells.  (+info)

Inhibitory effect of 4-aminopyridine on responses of the basilar artery to nitric oxide. (8/374)

1. Voltage-dependent K+ channels are present in cerebral arteries and may modulate vascular tone. We used 200 microM 4-aminopyridine (4-AP), thought to be a relatively selective inhibitor of voltage-dependent K+ channels at this concentration, to test whether activation of these channels may influence baseline diameter of the basilar artery and dilator responses to nitric oxide (NO) and cyclic GMP in vivo. 2. Using a cranial window in anaesthetized rats, topical application of 4-AP to the basilar artery (baseline diameter = 240+/-5 microm, mean +/- s.e.mean) produced 10+/-1% constriction. Sodium nitroprusside (a NO donor), acetylcholine (which stimulates endothelial release of NO), 8-bromo cyclic GMP (a cyclic GMP analogue), cromakalim (an activator of ATP-sensitive K+ channels) and papaverine (a non-NO, non-K+ channel-related vasodilator) produced concentration-dependent vasodilator responses that were reproducible. 3. Responses to 10 and 100 nM nitroprusside were inhibited by 4-AP (20+/-4 vs 8+/-2% and 51+/-5 vs 33+/-5%, respectively, n=10; P<0.05). Responses to acetylcholine and 8-bromo cyclic GMP were also partially inhibited by 4-AP. In contrast, 4-AP had no effect on vasodilator responses to cromakalim or papaverine. These findings suggest that NO/cyclic GMP-induced dilator responses of the basilar artery are selectively inhibited by 4-aminopyridine. 4. Responses to nitroprusside were also markedly inhibited by 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylate cyclase; 16+/-4 vs 1+/-1% and 44+/-7 vs 7+/-1%; n=10; P<0.05). 5. Thus, dilator responses of the rat basilar artery to NO appear to be mediated by activation of soluble guanylate cyclase and partially by activation of a 4-aminopyridine-sensitive mechanism. The most likely mechanism would appear to be activation of voltage-dependent K+ channels by NO/cyclic GMP.  (+info)

TY - JOUR. T1 - Cromakalim and cicletanine against pacing-induced myocardial ischemia in conscious rabbits. AU - Szilvássy, Z.. AU - Koltai, Matyas. AU - Ferdinándy, P.. AU - Jakab, Ildiko. AU - Lonovics, J.. AU - Tarrade, Thierry. AU - Allard, Michel. AU - Braquet, Pierre G.. PY - 1994. Y1 - 1994. N2 - Myocardial ischemia assessed by intracavital ST-segment elevation, shortening of ventricular effective refractory period (VERP), and increase in left ventricular end-diastolic pressure (LVEDP) was provoked by ventricular overdrive pacing (VOP) in conscious rabbits. Cromakalim (10 μg/kg), an ATP-sensitive K+ channel opener, and cicletanine (30 mg/kg), a cGMP-phosphodiesterase inhibitor, reduced VOP-induced ST-segment elevation and LVEDP-increase. Under resting conditions, cromakalim lowered blood pressure, increased heart rate (HR), and shortened VERP, whereas cicletanine decreased HR, prolonged VERP without changing blood pressure. Co-administration of cromakalim and cicletanine additively ...
Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)
Cromakalim | C16H18N2O3 | CID 443423 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.
The effects of trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin -1-yl)-7H- thieno[3,2-b]pyran (RWJ 26629) were compared with those of the standard potassium channel opener cromakalim and several standard calcium channel blockers. RWJ 26629 lowered the mean arterial blood pressure in conscious spontaneously hypertensive (ED30 = 10 micrograms/kg p.o. or 8 micrograms/kg i.v.) and renal hypertensive (15 ...
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Cromakalim (INN) is a potassium channel-opening vasodilator. The active isomer is levcromakalim. It acts on ATP-sensitive potassium channels and so causes membrane hyperpolarization. It can be used to treat hypertension as it will relax vascular smooth muscle to lower blood pressure. Hyperpolarisation of smooth muscle cell membranes pulls their membrane potential away from the threshold, so making it more difficult to excite them and thereby cause contraction. Reaction of 4-cyanophenol (4-Hydroxybenzonitrile) with 2-hydroxy-2-methyl-3-butyne under PTC probably proceeds to initial formation of a propargyl carbocation. The course of the reaction can be envisaged by assuming that this then attacks the aromatic ring; the resulting allylic cation can then capture the adjacent phenol oxygen and thus form the observed product (3). Treatment of that product with aqueous NBS leads to the addition of the elements of hypobromous acid and formation of the bromohydrin (4) as a mixture of the trans ...
The invention provides methods for determining the ability of compounds to regulate lipogenesis and lipolysis by acting as a sulfonylurea-1 (SUR 1) potassium channel activator, an adipocyte potassium channel activator, an SUR 1 antagonist, and an adipocyte specific SUR 1 antagonist. The present invention recognizes the presence of the sulfonylurea receptor in adipocytes and its utility in identifying compounds and in regulating lipogenesis and lipolysis.
Toxins that block voltage-dependent K(+) channels and those that modify Na(+) channel gating exhibit positive inotropic effect on skeletal muscle. We compared the effect of the venom of Tityus cambridgei (Tc) and Tityus serrulatus (Ts) scorpions on mouse diaphragm force, in vitro. In indirect and direct (using D-tubocurarine 7.3 mu M) stimulation, Tc, 10 mu g/mL increased the contractile force, an effect prevented by tetrodotoxin (TTX) while Ts, 0.5 mu g/mL, potentiated only indirectly stimulated diaphragm, thus indicating its activity is mainly mediated through acetylcholine release from nerve terminal. This effect is prevented by TTX and attenuated by the K(+) channel opener cromakalim. In conclusion, our data show that while the positive inotropic effect of both venoms appears associated to the activity of Na(+) and K(+) channels, only Tc venom acts also directly on skeletal muscle. This finding call for further studies on Tc venom to identify the toxin responsible for its direct inotropic ...
Purpose : To evaluate the pharmacologic and safety parameters of CKLP1 following topical application in hound dog eyes. Methods : Optimal concentration of CKLP1 for reduction of IOP was established in female hound dogs (n=5) by topical application to the eye with CKLP1 (5-20 mM). Following washout (14 days), the dogs were treated with the optimal dose once daily for 60 consecutive days. IOP was measured 3 times daily (1, 4 and 23 hours post treatment), 3-7 times per week. Blood pressure measurements were recorded using a tail cuff, once daily, 3-5 times per week. For pharmacokinetic studies, both eyes were treated with CKLP1 for 8 consecutive days. Blood samples were collected on days 1, 4 and 8 and concentration of CKLP1 and its parent compound levcromakalim were evaluated in the plasma by LC MS/MS. Necropsy was performed on all animals and systemic effects of drug administration were histologically evaluated in 40 different tissue samples from each animal. Results : The 10 mM topical dose of ...
Experimental and clinical studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid‑onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade (L‑calcium channel) and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra‑rapid potassium channel‑operated current. Testosterone improves cardiac output, functional exercise capacity, VO2max and vagally mediated arterial baroreceptor cardiac reflex sensitivity in chronic heart failure. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance ...
[150 Pages Report] Check for Discount on 2016 Minoxidil sulphate (CAS 83701-22-8) Industry Market Report report by Prof Research. The Global and Chinese Minoxidil sulphate Industry, 2011-2021 Market...
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The 203/266 Replacement Part Kit is for the electric can opener. The Kit contains 1 gear, 1 knife and 1 stud. Make sure the can opener is performing a
The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one potassium channel activator, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses
The present invention describes novel nitrosated and/or nitrosylated potassium channel activators, and novel compositions comprising at least one nitrosated and/or nitrosylated potassium channel activator, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one potassium channel activator, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses
(2015) Sun et al. Frontiers in Neurology. High dose sodium salicylate causes moderate, reversible hearing loss and tinnitus. Salicylate-induced hearing loss is believed to arise from a reduction in the electromotile response of outer hair cells (OHCs) and/or reduction of KCNQ4 potassium currents ...
Effects of KRN4884 (5-amino-,i,N,/i,-[2-(2-chlorophenyl)ethyl]-,i,N,/i,-cyano-3-pyridinecarboxamidine), a novel K,sup,+,/sup, channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K,sup,+,/sup, bathing solution, KRN4884 elicited an outward current at −30 mV. KRN4884-induced current had a reversal potential of −78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K,sup,+,/sup, current (I,sub,K-ATP,/sub,). On the other hand, KRN4884 affected neither voltage-dependent Ca,sup,2+,/sup, nor delayed rectifier K,sup,+,/sup, channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K,sup,+,/sup, solution, KRN4884 activated 47 pS K,sup,+,/sup, channels in the presence of adenosine diphosphate. Similar 47 pS K,sup,+,/sup, ...
Lee Sang Eok , Han Ji Young , Kim Hyun Woo , Yang In Jun , Xu Wen-Xie , Lee Sang Jin , Kim Young Chul , Yun Hyo-Yung , Kim Dae Hoon , Son Seung Myeung , Choi Song-Yi , You Ra Young , Kim Chan Hyung , Choi Woong , Kim Hun Sik , Lim Yung Ji … channel opener, suppressed contractions to 30% (basal tone to −0.2 g) of the control. … The inhibitory effect of pinacidil on contraction was reversed to 59% of the control by glibenclamide (20 μM), a K,sub,ATP,/sub, … Pinacidil also inhibited the acetylcholine (ACh)-induced tonic and phasic contractions in a glibenclamide-sensitive manner (42% and 6% of the control, respectively). … Journal of Smooth Muscle Research 56(0), 29-45, 2020 J-STAGE ...
Easy Comforts hands free can opener is a simple way to open cans. Automatic can opener walks around the rim, leaving smooth edges. Uses 2 AA batteries.
Simple question. Does 4-piece change how you go about opening? Personally I prefer SV but have gotten my BM play to a point where I should be using it as it outperforms SV in certain encounters. Still struggle with the opener a bit and recently picked up 4-piece. Thanks in advance for any input.
TY - JOUR. T1 - The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. AU - McFalls, Edward O.. AU - Kelly, Rosemary F.. AU - Hu, Qingsong. AU - Mansoor, Abdul. AU - Lee, Joseph. AU - Kuskowski, Michael. AU - Sikora, Joseph. AU - Ward, Herbert B.. AU - Zhang, Jianyi. PY - 2007/11. Y1 - 2007/11. N2 - Within hibernating myocardium, it is uncertain whether a normal energetic state is present at baseline and whether maintaining that energy state during a catecholamine challenge is dependent on ATP-dependent potassium channel opening. In this study, 16 swine underwent a thoracotomy with placement of an external constrictor on the left anterior descending coronary artery (LAD) (hibernation model). Seven additional swine underwent a sham operation. At 10 wk, the myocardial energetic state in the LAD region was assessed by 31P-NMR spectroscopy, and the ratio of phosphocreatine to ATP (PCr/ATP) was ...
There has been much recent interest in the roles played by smooth-muscle K+ channels in protecting cells against ischemic and anoxic insults and in therapeutic vaso- and bronchodilation (Buckingham 1990; Longmore & Weston 1990). A K+ channel, which is uniquely sensitive to cytoplasmic ATP (KATP), has been identified as a likely candidate for mediating these important functions (Standen et al. 1989). We now show, by using electrophysiological techniques in three different types of smooth muscle, that a large-conductance voltage and Ca2+ -sensitive channel, otherwise indistinguishable from the large-conductance Ca2+ -activated K+ channel (BK channel), is also sensitive to cytoplasmic ATP and cromakalim. ATP, in a dose-dependent manner, decreased the probability of channel opening (P0) of rabbit aortic, rabbit tracheal and pig coronary artery BK channels with a K1 of 0.2-0.6mM. Cromakalim, 10 μM, partially reversed the ATP induced inhibition and increased P0. Our observations raise the possibility ...
McCloskey, Conor, Bailey, Elizabeth H., Zhang, J. (Jie), Shmygol, Anatoly, Thornton, Steven, Catalano, Roberto D., England, Sarah, Rada, Cara and Blanks, Andrew M. (2011) The novel potassium channel Kir7.1 is a critical component of uterine quiescence in mice and human. Reproductive Sciences, Vol.18 (No.3). 159A-159A ...
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Synopsis Nicorandil belongs to the class of compounds known as potassium channel activators which are characterised by their arterial vasodilator properties. In addition, nicorandil has venodilating...
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Once again the opening sequence of Copper is a well crafted little gem that represents the best the show has to offer in terms of style and staging, and this weeks opener is even more intriguing than usual thanks to a delightfully strange departure in tone. Rather than start with a wide action setpiece such as the…
Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segreg …
Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K+ channels, indicating that oxygen-derived free radicals may activate these channels. Levels of free radicals are increased throughout the arterial wall in animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive K+ channels may be augmented in chronic hypertension. The present study was designed to determine whether relaxations to an ATP-sensitive K+ channel opener, levcromakalim, are increased in the aorta from spontaneously hypertensive rats (SHR) and whether free radical scavengers reduce these relaxations. Rings of aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR were suspended for isometric force recording. Relaxations to levcromakalim (10(-8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented in the aorta from SHR, compared to those in the aorta from WKY. In the aorta from SHR, catalase (1200 U/ml), but neither superoxide dismutase (150 U
Read Kinetic Analysis of the Inhibitory Effect of Glibenclamide on KATP Channels of Mammalian Skeletal Muscle, The Journal of Membrane Biology on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
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Glibenclamide Tablet is a medicine that is used for the treatment of Type 2 Diabetes Mellitus and other conditions. Glibenclamide Tablet contains Glibenclamide
BAYK 8644 is a L-type Ca2+ channel activator (EC50 = 17.3 nM). BAYK 8644 has positive inotropic, vasoconstrictive and behavioral effects in vivo.
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... (INN) is a potassium channel-opening vasodilator. The active isomer is levcromakalim. It acts on ATP-sensitive ...
"Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and ...
Traditional Bangladeshi healers use the bark as an antidiarrhoeal as it contains an antispasmodic similar to cromakalim. The ...
... cromakalim MeSH D03.438.150.500 - ellagic acid MeSH D03.438.150.600 - hematoxylin MeSH D03.438.150.909 - vitamin e MeSH D03.438 ... cromakalim MeSH D03.830.219.500 - ellagic acid MeSH D03.830.219.600 - hematoxylin MeSH D03.830.219.909 - vitamin e MeSH D03.830 ... cromakalim MeSH D03.383.129.578.399 - maleimides MeSH D03.383.129.578.399.418 - ethylmaleimide MeSH D03.383.129.578.617 - ...
Crolom Cromolyn cromakalim (INN) cromitrile (INN) cromoglicate lisetil (INN) cromoglicic acid (INN) Cromoptic cronidipine (INN ...
Comment: The INN-assigned compound cromakalim is a mixture of enantiomers (Click here to view the related PubChem records). The ...
Vasodilator effects of cromakalim and HA 1077 in diabetic rat aorta. Swiss Med Wkly. 2012;142:w13558. ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
Ma, H., Folmes, C. D. L., Wu, J., Morey, R., Mora-Castilla, S., Ocampo, A., Ma, L., Poulton, J., Wang, X., Ahmed, R., Kang, E., Lee, Y., Hayama, T., Li, Y., Van Dyken, C., Gutierrez, N. M., Tippner-Hedges, R., Koski, A., Mitalipov, N., Amato, P., & 6 othersWolf, D. P., Huang, T., Terzic, A., Laurent, L. C., Belmonte, J. C. I. & Mitalipov, S., Aug 13 2015, In: Nature. 524, 7564, p. 234-238 5 p.. Research output: Contribution to journal › Article › peer-review ...
... whereas cromakalim showed little selectivity. In addition to increasing the time to the onset of contracture, BMS-191095 ... which is comparable to 4.7 μM and 3.0 μM for cromakalim and BMS-180448, respectively. Comparisons of cardioprotective and ... which retain the cardioprotective activity of agents such as cromakalim while being significantly less potent as vasodilators. ...
Antiulcer activity of cromakalim against experimentally induced gastric and duodenal ulcers in rats and guinea pigs. J. Pharm. ...
Effects of cromakalim (BRL 34915) on mechanical responses of rat vas deferens to noradrenaline and naphazoline. Grana, E., ... Inhibition by glibenclamide of the effects of cromakalim on responses of rat vas deferens to naphazoline. Grana, E., Barbieri, ... Cromakalim has been shown to inhibit naphazoline-induced contractions and spontaneous activity induced by exposure to ...
Activation of IK-ATP with cromakalim resulted in uncoupling at 23.3(1.9) min (p < 0.002 v control). Glibenclamide without ... APD80 during ischaemia was significantly shorter in the preconditioning and cromakalim groups than in the control group from 5 ... cromakalim (BRL 34915), an opener of IK-ATP; (5) sustained ischaemia after 10 min perfusion with 20 microM glibenclamide ...
Cromakalim, (3R-cis)-Isomer. Cromakalim, (3R-trans)-Isomer. Cromakalim, (3S-cis)-Isomer. Cromakalim, (3S-trans)-Isomer. ... Cromakalim - Preferred Concept UI. M0029396. Scope note. A potassium-channel opening vasodilator that has been investigated in ... Cromakalim, (trans)-Isomer. Lemakalim. Levcromakalim. Tree number(s):. D03.383.129.578.150. D03.383.663.283.455. D03.633. ... Cromakalim Entry term(s):. BRL 38226. BRL 38227. BRL-34915. BRL-38226. BRL-38227. BRL38226. BRL38227. ...
... cromakalim > N-(4-benzoyl phenyl)-3,3,3-trifluro-2-hydroxy-2-methylpropionamine (ZD6169) > 9-(3-cyanophenyl)-3,4,6,7,9,10- ...
4-Aminopyridine, Animals, Benzopyrans, Carbamazepine, Cromakalim, Electric Conductivity, Nervous System, Parasympatholytics, ...
Adenosine Triphosphate, Animals, Binding Sites, Cromakalim, Diazoxide, Humans, Minoxidil, Nicorandil, Pinacidil, Potassium ...
Influence of Cromakalim, $K^+$. Channel Opener, and Glibenclamide, $K^+$. Channel Blocker, on Intestinal Movements in Rabbit ... This study was attempted to investigate the effects of cromakalim (CRK), $K^{+}$. channel opener, and glibenclamide (GLY), $K ...
Cromakalim. Humans. Infusions, Intravenous. Male. Potassium Channels.drug effects. Pyrroles.pharmacology. Spinal Cord Injuries. ...
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Stimulation of renin secretion by potassium-channel activation with cromakalim. European journal of clinical pharmacology 36 (5 ...
Synthesis and conformational analysis of a series of 1-benzopyrano[3,4-b][1,4]oxazines structurally related to cromakalim.. ...
The increases in CBF by cromakalim were dose dependent. Glibenclamide blunted the increases in CBF caused by cromakalim and ... Cromakalim caused modest, dose-dependent decreases in SS, although MVO2did not change consistently (Table 5). Glibenclamide ... Furthermore, it has been shown that various drugs, such as cromakalim, may modulate the opening of the KATPchannels. [8,9] ... Table 5. Effect of Intracoronary Infusion of Cromakalim at 2.5 and 5.0 micro gram/min (CROM-2.5 and CROM-5.0, respectively) on ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. HN - 2008 ...
  • The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel-independent vasodilators, sodium nitroprusside and acetylcholine. (silverchair.com)
  • This study was attempted to investigate the effects of cromakalim (CRK), $K^{+}$ channel opener, and glibenclamide (GLY), $K^{+}$ channel blocker, on intestinal function of rabbit. (koreascience.kr)
  • Comparisons of cardioprotective and vasorelaxant potencies in vitro and in vivo showed BMS-191095 to be significantly more selective for cardioprotection with virtually no effect on peripheral smooth muscle, whereas cromakalim showed little selectivity. (aspetjournals.org)
  • KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate. (jefferson.edu)
  • 1. The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. (epfl.ch)
  • By contrast pinacidil (10-20 microg per mouse i.c.v.), minoxidil (10-20 microg per mouse i.c.v.) and cromakalim (20-30 microg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. (epfl.ch)
  • Feleder E.C, Adler-Graschinsky E. Endothelium-mediated and N omega-nitro-L-arginine methyl ester-sensitive responses to cromakalim and diazoxide in the rat mesenteric bed. (kiev.ua)
  • The K ATP COs typified by pinacidil are sensitive to L-arginine analogues whereas the K ATP COs typified by cromakalim are insensitive to L-arginine analogues. (shu.ac.uk)
  • This sensitivity appears to be independent of nitric oxide synthase (NOS) action as the vasorelaxant and Rb efflux responses to pinacidil are insensitive to the NOS inhibitor L-N5-(1-iminoethyl) ornithine (L-NIO).Pinacidil and cromakalim are believed to have a degree of commonality in how they interact with the K ATP CO binding site on SUR2B. (shu.ac.uk)
  • In contrast, cromakalim is not believed to interact with this particular region of the K ATP CO binding site, which explains the insensitivity of cromakalim to L-NAME. (shu.ac.uk)
  • Michael Fautsch, Ph.D. , and others tested cromakalim in mouse and human models alone and in combination with latanoprost-free acid. (mayoclinic.org)
  • Mayo researchers have shown that the K-ATP channel opener cromakalim has potential as a hypotensive agent to lower intraocular pressure. (mayoclinic.org)
  • 6. A novel cromakalim analogue induces cell cycle arrest and apoptosis in human cervical carcinoma HeLa cells through the caspase- and mitochondria-dependent pathway. (nih.gov)