Nitric oxide limits the eicosanoid-dependent bronchoconstriction and hypotension induced by endothelin-1 in the guinea-pig.
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1. This study attempts to investigate if endogenous nitric oxide (NO) can modulate the eicosanoid-releasing properties of intravenously administered endothelin-1 (ET-1) in the pulmonary and circulatory systems in the guinea-pig. 2. The nitric oxide synthase blocker N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM; 30 min infusion) potentiated, in an L-arginine sensitive fashion, the release of thromboxane A2 (TxA2) stimulated by ET-1, the selective ET(B) receptor agonist IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1(8-21)) or bradykinin (BK) (5, 50 and 50 nM, respectively, 3 min infusion) in guinea-pig isolated and perfused lungs. 3. In anaesthetized and ventilated guinea-pigs intravenous injection of ET-1 (0.1-1.0 nmol kg(-1)), IRL 1620 (0.2-1.6 nmol kg(-1)), BK (1.0-10.0 nmol kg(-1)) or U 46619 (0.2-5.7 nmol kg(-1)) each induced dose-dependent increases in pulmonary insufflation pressure (PIP). Pretreatment with L-NAME (5 mg kg(-1)) did not change basal PIP, but increased, in L-arginine sensitive manner, the magnitude of the PIP increases (in both amplitude and duration) triggered by each of the peptides (at 0.25, 0.4 and 1.0 nmol kg(-1), respectively), without modifying bronchoconstriction caused by U 46619 (0.57 nmol kg(-1)). 4. The increases in PIP induced by ET-1, IRL 1620 (0.25 and 0.4 nmol kg(-1), respectively) or U 46619 (0.57 nmol kg(-1)) were accompanied by rapid and transient increases of mean arterial blood pressure (MAP). Pretreatment with L-NAME (5 mg kg(-1); i.v. raised basal MAP persistently and, under this condition, subsequent administration of ET-1 or IRL 1620, but not of U-46619, induced hypotensive responses which were prevented by pretreatment with the cyclo-oxygenase inhibitor indomethacin. 5. Thus, endogenous NO appears to modulate ET-1-induced bronchoconstriction and pressor effects in the guinea-pig by limiting the peptide's ability to induce, possibly via ET(B) receptors, the release of TxA2 in the lungs and of vasodilatory prostanoids in the systemic circulation. Furthermore, it would seem that these eicosanoid-dependent actions of ET-1 in the pulmonary system and on systemic arterial resistance in this species are physiologically dissociated. (+info)
The Janus-faced aspect of 'dry weight'.
(2/1770)
BACKGROUND: The goal of haemodialysis treatment in end-stage renal disease (ESRD) patients is to correct the complications of the uraemic condition. Among the main complications are fluid overload and subsequent hypertension that are corrected by achievement of 'dry weight'. We report in this study the evolution of post-dialysis body-weight and blood pressure in patients who began their HD treatment in our unit. METHODS: We studied the monthly evolution of post-dialysis body-weight (expressed as a percentage of pre-dialysis body-weight at the first HD treatment) and predialysis mean arterial pressure (MAP) over 24 months in 61 patients (21 females, mean age 59.8 years; 20% diabetic), treated with cellulosic membranes for 8 h, 3 times a week. RESULTS: The post-dialysis body-weight decreased between the onset of HD and month 2 (M2) (-4.40+/-0.52%). Then it went up, reaching -1.56+/-0.96% at M6, +0.3+/-1.27% at M12, +1.27+/-1.38% at M18 and +1.64+/-1.33% at M24. The post-dialysis body-weight increased by 6% between M2 and M24. The mean arterial pressure (MAP) decreased from 111.3+/-2.5 mmHg at M0 to 94.4+/-1.7 at M6, and then remained stable after M6. Between M2 and M6 the post-dialysis body-weight increased, whereas the predialysis MAP continued to decline. The incidence of hypotension episodes was maximal during the first 4 months of HD treatment. CONCLUSIONS: After the second month of dialysis treatment, the simultaneous increase of post-dialysis body-weight and decrease of pre-dialysis MAP are related to the effects of two processes, i.e. increased weight as the result of anabolism induced by the HD treatment on the one hand and normalization of blood pressure by fluid removal on the other. Continuous clinical assessment of the patient is necessary to provide adequate prescription of post-dialysis body-weight. During the first months of HD treatment, the nephrologist, like Janus, is a double-faced gatekeeper: he must be willing to decrease post-dialysis weight to achieve 'dry weight' and to normalize blood pressure, but he must also be prepared to increase it to compensate for anabolism and to avoid episodes of hypotension. (+info)
Hypotension induced by exercise is associated with enhanced release of adenyl purines from aged rat artery.
(3/1770)
To determine whether the antihypertensive effects of exercise are associated with release of ATP and its metabolites from arteries, we assayed blood pressure and the release of adenine nucleotides and nucleosides from the caudal arteries of exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill for 12 wk significantly decreased the rise in systolic and diastolic blood pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of oleic, linoleic, and linolenic acids in the caudal artery decreased significantly with exercise, demonstrating an association between exercise and the unsaturation index of caudal arterial fatty acids. The amounts of total adenyl purines released by the arterial segments from exercised rats, both spontaneously and in response to norepinephrine, were significantly greater by 80.0 and 60.7%, respectively, than those released by tissues from sedentary rats. These results suggest that exercise alters the membrane fatty acid composition in aged rats as well as the release of ATP from vascular endothelial cells and that these factors are associated with the regression of the rise in blood pressure normally observed with advanced age. (+info)
Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss).
(4/1770)
The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines. (+info)
Sudden death in hypertrophic cardiomyopathy: potential importance of altered autonomic control of vasculature.
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Current evidence suggests that alterations in the autonomic function and abnormal vascular control play a significant role either as independent triggers themselves or as modifiers of ischaemia and tolerance to to arrhythmias. A combination of several factors--that is, arrhythmia, hypotension, altered autonomic function including vascular control, and ischaemia are therefore likely to act as triggers for sudden death. The relative contribution of each of these factors needs further detailed study. (+info)
Effects of isoflurane anesthesia on pulmonary vascular response to K+ ATP channel activation and circulatory hypotension in chronically instrumented dogs.
(6/1770)
BACKGROUND: The objective of this study was to evaluate the effects of isoflurane anesthesia on the pulmonary vascular responses to exogenous adenosine triphosphate-sensitive potassium (K+ ATP) channel activation and circulatory hypotension compared with responses measured in the conscious state. In addition, the extent to which K+ ATP channel inhibition modulates the pulmonary vascular response to circulatory hypotension in conscious and isoflurane-anesthetized dogs was assessed. METHODS: Fifteen conditioned, male mongrel dogs were fitted with instruments for long-term monitoring to measure the left pulmonary vascular pressure-flow relation. The dose-response relation to the K+ ATP channel agonist, lemakalim, and the pulmonary vascular response to circulatory hypotension were assessed in conscious and isoflurane-anesthetized (approximately 1.2 minimum alveolar concentration) dogs. The effect of the selective K+ ATP channel antagonist, glibenclamide, on the pulmonary vascular response to hypotension was also assessed in conscious and isoflurane-anesthetized dogs. RESULTS: Isoflurane had no effect on the baseline pulmonary circulation, but it attenuated (P<0.05) the pulmonary vasodilator response to lemakalim. Reducing the mean systemic arterial pressure to approximately 50 mm Hg resulted in pulmonary vasoconstriction (P<0.05) in the conscious state, and this response was attenuated (P<0.05) during isoflurane. Glibenclamide had no effect on the baseline pulmonary circulation, but it potentiated (P<0.05) the pulmonary vasoconstrictor response to hypotension in conscious and isoflurane-anesthetized dogs. CONCLUSIONS: These results indicate that K+ ATP-mediated pulmonary vasodilation and the pulmonary vasoconstrictor response to hypotension are attenuated during isoflurane anesthesia. Endogenous K+ ATP channel activation modulates the pulmonary vasoconstrictor response to hypotension in the conscious state, and this effect is preserved during isoflurane anesthesia. (+info)
Spike generation from dorsal roots and cutaneous afferents by hypoxia or hypercapnia in the rat in vivo.
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The present study aimed at investigating the responsiveness of different parts of the primary afferent neurones to a brief hypoxia, hypercapnia or ischaemia under in vivo conditions. Action potentials were recorded in separate groups of anaesthetized rats from (i) the peripheral end of the central stump of the cut L3, L4 or L5 dorsal root (dorsal root preparation); (ii) the central end of the peripheral stump of the cut saphenous nerve (saphenous-receptor preparation); (iii) the distal end of a segment of the saphenous nerve cut at both ends (axon preparation). In paralysed animals interruption of artificial ventilation for 20-60 s elicited or increased the frequency of action potentials in both the dorsal root and saphenous-receptor preparations. Activation of these preparations was also achieved by inspiration of gas mixtures containing 10-0% oxygen (mixed with nitrogen) or 20-50% carbon dioxide (mixed with oxygen) which elicited in the blood a decrease in PO2 or an increase in PCO2 with a fall in pH. Occlusion of the femoral artery for 3 min also caused spike generation in the saphenous-receptor preparations with little alteration in blood pressure. All these stimuli failed to evoke action potentials in the axon preparations. Systemic (300 mg kg-1 s.c.) or perineural (2%) capsaicin pretreatment failed to inhibit the effect of hypoxia, hypercapnia or ischaemia, indicating a significant contribution of capsaicin-insensitive neurones to the responses. It is concluded that central and peripheral terminals but not axons of primary afferent neurones are excited by a brief hypoxia or hypercapnia and the peripheral terminals by a short local ischaemia as well. Excitation of central terminals by hypoxia or hypercapnia revealed in this way an antidromic activation of dorsal roots in response to natural chemical stimuli. (+info)
Effects of phosphodiesterase inhibitors after coronary artery bypass grafting.
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The aim of this study was to estimate the postoperative effects of phosphodiesterase (PDE) inhibitors (milrinone and olprinone) after coronary artery bypass grafting (CABG). To prevent hypotension caused by the PDE inhibitors, low dose of catecholamines were used concomitantly. A total of 34 elective CABG cases were tested. In 12 cases, 0.25 microg kg(-1) min(-1) of milrinone, 3 microg kg(-1) min(-1) of dobutamine (DOB) and dopamine (DOA) were used concomitantly (Group-M). In another 10 patients, 0.1 microg kg(-1) min(-1) of olprinone and the same doses of the catecholamines were infused (Group-O). As a control, the same doses of DOA and DOB only were administered in 12 patients (Group-C). When the pump flow of the cardiopulmonary bypass (CPB) decreased to half, these drugs were given in all groups. Hemodynamics were recorded before CPB, just after the operation, and 3, 6, 12, 24, 48 and 72 h after the operation. Both milrinone and olprinone increased the cardiac index and decreased systemic vascular resistance to almost the same degree. Olprinone decreased mean aortic and pulmonary artery pressures, and also significantly reduced the preload of both right and left heart compared with milrinone. Significant hypotension was not detected due to the concomitant usage of low-dose catecholamines. This concomitant usage of PDE inhibitors and catecholamines allowed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. Good oxygen demand and supply balance were maintained in peripheral tissue. These results suggest that these new PDE inhibitors may be effective not only for weaning from CPB but also for post-cardiotomy cardiogenic shock. (+info)