Pentobarbital-sensitive EDHF comediates ACh-induced arteriolar dilation in the hamster microcirculation.
It is unclear to what extent the endothelium-derived hyperpolarizing factor (EDHF) contributes to the control of microcirculatory blood flow in vivo. We analyzed, by intravital microscopy in hamster muscles, the potential role of EDHF along the vascular tree under stimulated (ACh) or basal conditions. Experiments were performed in conscious as well as anesthetized (pentobarbital, urethan) animals. Additionally, cellular effects of the potential EDHF were studied in isolated small arteries. In pentobarbital-anesthetized animals, treatment with Nomega-nitro-L-arginine (L-NNA; 30 micromol/l) and indomethacin (3 micromol/l) reduced the dilation in response to 10 micromol/l ACh from 60 +/- 6 to 20 +/- 4%. This nitric oxide/prostaglandin-independent dilation (NPID), which was of a similar magnitude in large and small arterioles, was abolished by potassium depolarization or charybdotoxin (ChTX, 1 micromol/l) but not by glibenclamide. In conscious animals, NPID amounted to 33 +/- 3%. The inhibitor of the P-450 monooxygenase 17-octadecynoic acid (ODYA) reduced NPID further to 9 +/- 4%. ChTX abolished the NPID and also reduced basal diameters (by -11 +/- 3%). The induction of anesthesia with pentobarbital reduced NPID (to 12 +/- 6%), whereas urethan anesthesia was without effect. Pentobarbital also reduced the ACh-induced hyperpolarization of vascular smooth muscle in isolated arteries, whereas ChTX abolished it. This study suggests that a considerable part of the ACh dilation in the microcirculation is mediated by EDHF, which also contributes to the control of basal tone in conscious animals. The direct inhibitory effect of pentobarbital and ODYA supports the idea that "microcirculatory" EDHF is a product of the cytochrome P-450 pathway. The role of EDHF might be underestimated in pentobarbital-anesthetized animals. (+info)
Dose effect and benefits of glycopyrrolate in the treatment of bradycardia in anesthetized dogs.
This study evaluated the effectiveness of glycopyrrolate (0.005 or 0.01 mg/kg body weight (BW)) in anesthetized dogs (n = 40) for reversal of bradycardia (< 65 beats/min). Following random intravenous (i.v.) treatment, heart rate was determined at 5 min and, if it was < or = 70 beats/min, the lower dose was repeated. A 2-way analysis of variance considered dose and animal size (< or = 10 kg, > 10 kg) effects (P < 0.05). Glycopyrrolate produced a significant increase in heart rate and infrequent tachycardia (< or = 150 beats/min), which was not dose-related. The size of the dog produced a significant effect on baseline heart rate (higher in small), rate following the first dose (lower in small), and requirement for retreatment (47% in small, 13% in large). In a separate group of anesthetized dogs (n = 20), the blood pressure effect of glycopyrrolate (0.01 mg/kg BW, i.v.) treatment of bradycardia (65-85 beats/min, weight-adjusted) was studied. A significant increase in systolic, diastolic, and mean blood pressure was produced. In conclusion, the effective dose of glycopyrrolate treatment is size-related and produces a beneficial effect on blood pressure. (+info)
Dual effects of pentobarbital on rat sacral dorsal commissural neurons in vitro.
AIM: To study the effects of pentobarbital (PB) on acutely dissociated rat sacral dorsal commissural neurons (SDCN). METHODS: Nystatin-perforated patch clamp recording was used. RESULTS: (1) At a holding potential of -40 mV, PB induced inward Cl- current (IPB) in a concentration-dependent manner with a EC50 (95% confidence limits) of 416 (385-477) mumol.L-1 and a Hill coefficient of 1.08. (2) Picrotoxin reversibly blocked IPB. (3) The reversal potential of IPB was close to the Cl- equilibrium potential. (4) PB enhanced GABA-induced Cl- influx (IGABA). In the presence of PB 30 mumol.L-1, the EC50 (95% confidence limits) of IGABA decreased from 6.9 (5.4-8.4) mumol.L-1 to 3.5 (2.9-4.1) mumol.L-1. CONCLUSION: PB had dual effects on SDCN, facilitated GABAA receptor-mediated currents and at higher concentrations induced Cl- influx itself. (+info)
Glucocorticoid effects on mesotelencephalic dopamine neurotransmission.
Multiple neurochemical estimates were used to examine peripheral corticosterone (CORT) effects in dopaminergic terminal regions. Acute CORT administration, which elevated plasma CORT (5 h), slightly decreased dihydroxyphenylacetic acid (DOPAC) to dopamine (DA) ratios in the striatum but not in other regions examined. Two weeks of adrenalectomy (ADX) increased both medial prefrontal cortex DOPAC/DA and homovanillic acid (HVA)/DA and striatal HVA/DA. A reciprocal pattern of changes was observed with CORT replacement in ADX animals. In contrast, CORT replacement in ADX animals did not significantly influence tyrosine hydroxylase content, basal dihydroxyphenylalanine (DOPA) accumulation after NSD 1015 treatment or the decline in DA after alpha-methyl-para-tyrosine, suggesting that neither DA neuronal activity nor release are altered by CORT. Moreover, neither gamma-hydroxybutyric acid lactone-induced increases in DOPA accumulation or stress-induced increases in DA utilization were influenced by CORT replacement, indicating that neither autoreceptor regulation of DA synthesis nor acute stress regulation of DA utilization are changed by CORT. The findings are most consistent with direct inhibition of basal DA metabolism in the medial prefrontal cortex and striatum. The possible physiological and behavioral significance of this inhibition is being further explored. (+info)
Gamma-hydroxybutyrate and cocaine administration increases mRNA expression of dopamine D1 and D2 receptors in rat brain.
The effects of acute and repeated gamma-hydroxybutyrate (GHB) and cocaine administration on D1 and D2 dopamine receptor mRNA expression were examined using in situ hybridization histochemistry in different rat brain structures rich in GHB receptors. Six hours after a single GHB administration (500 mg/kg i.p.), an increase in D1 and D2 mRNA expression was observed in almost all regions examined; whereas, acute cocaine injection (20 mg/kg i.p.) had no effect. Repeated exposure to GHB (500 mg/kg i.p. twice daily) for 10 days, followed by a 14-h withdrawal period, induced increasing effects on D1 and D2 dopamine receptor mRNA expression, similar to those caused by chronic treatment with cocaine (20 mg/kg i.p. once a day). These effects of GHB and cocaine on dopamine receptor mRNA expression could be a consequence, for both compounds, of the modulation of dopaminergic activity; thus, supporting the benefit of GHB in cocaine substitution therapy. (+info)
Echocardiographic assessment of cardiac function in conscious and anesthetized mice.
Using a high-frequency linear transducer (15L8), we studied 1) the feasibility of performing echocardiography in nonanesthetized mice compared with mice given pentobarbital sodium (Pento) or a mixture of ketamine and xylazine and 2) the feasibility of echocardiographic evaluation of left ventricular (LV) hypertrophy, dilatation, and function in mice with two-kidney, one-clip hypertension or myocardial infarction (MI). Heart rate (HR) in awake mice was 658 +/- 9 beats/min; Pento and ketamine plus xylazine reduced HR to 377 +/- 11 and 293 +/- 19 beats/min, respectively, associated with a significant decrease in shortening fraction (SF), ejection fraction (EF), and cardiac output (CO) and an increase in LV end-diastolic (LVEDD) and end-systolic dimensions (LVESD). Mice with 4 wk of two-kidney, one-clip hypertension had increased LV mass (15.62 +/- 0. 62 vs. 22.17 +/- 1.79 mg) without altered LV dimensions, SF, EF, or CO. Mice studied 4 wk post-MI exhibited obvious LV dilatation and systolic dysfunction, as evidenced by increased LVEDD and LVESD and decreased SF, EF, and CO. Our findings clearly show the adverse impact of anesthesia on basal cardiac function and the difficulty in interpreting data obtained from anesthetized mice. We believe this is the first study to demonstrate the feasibility of using echocardiography to assess cardiovascular function in the nonanesthetized mouse. (+info)
Antinociceptive effect of R-(+)-hyoscyamine on the conjunctival reflex test in rabbits.
R-(+)-Hyoscyamine (1-10 microg/kg, s.c.) dose-dependently increased the local anesthetic effect of procaine (50 microg/ml) and lidocaine (50 microg/ml) in the conjunctival reflex test in the rabbit. This potentiating effect is completely prevented by the M1 antagonist dicyclomine (10 mg/kg, s.c.). The intensity of R-(+)-hyoscyamine antinociception was comparable to that induced by morphine (2 mg/kg, s.c.) and minaprine (15 mg/kg, s.c.), used as analgesic reference drugs. In the same experimental conditions, the S-(-)-enantiomer of atropine (0.1-10 microg/kg, s.c.), was completely ineffective. The present results confirm the ability of R-(+)-hyoscyamine to produce a paradoxical antinociceptive effect mediated by a cholinergic mechanism not only in rodents but also in the rabbit. (+info)
Closed-loop control of propofol anaesthesia.
We describe the use of a closed-loop system to control depth of propofol anaesthesia automatically. We used the auditory evoked potential index (AEPindex) as the input signal of this system to validate it as a true measure of depth of anaesthesia. Auditory evoked potentials were acquired and processed in real time to provide the AEPindex. The AEPindex was used in a proportional integral (PI) controller to determine the target blood concentration of propofol required to induce and maintain general anaesthesia automatically. We studied 100 spontaneously breathing patients. The mean AEPindex before induction of anaesthesia was 73.5 (SD 17.6), during surgical anaesthesia 37.8 (4.5) and at recovery of consciousness 89.7 (17.9). Twenty-two patients required assisted ventilation before incision. After incision, ventilation was assisted in four of these 22 patients for more than 5 min. There was no incidence of intraoperative awareness and all patients were prepared to have the same anaesthetic in future. Movement interfering with surgery was minimal. Cardiovascular stability and overall control of anaesthesia were satisfactory. (+info)