RELAXATION OF RABBIT CEREBRAL-ARTERIES INVITRO BY CLONIDINE - EVIDENCE OF H2-RECEPTOR MEDIATION
- 1 January 1983
- journal article
- research article
- Vol. 265 (2) , 259-273
Abstract
The action of the antihypertensive agent, clonidine, was studied in a perfused preparation of rabbit middle cerebral arteries (MCA) in vitro. The MCA segments (8 mm long) were perfused at constant flow, the perfusion pressure upstream being monitored as an index of smooth muscle tone. In both normal (K+ = 2.7 mM) and high potassium (K+ = 30 mM) solutions, clonidine (3.10-10-10-4 mol/l) relaxed the arteries in a concentration-dependent manner. Expressed as a percentage of the maximum relaxation obtained in normal and high K+ solution with 10-4 mol/l papaverine, the Em [maximum response] was 79 .+-. 3.9% (mean .+-. SEM [standard error of the mean]) and 63.7 .+-. 2.4%, respectively, and the EC 50 [median effective concentration] (4.3 .+-. 2.0) 10-8 mol/l and (1.3 .+-. 1.0) 10-8 mol/l, respectively. The action of 6 specific antagonists at 3.106 mol/l was tested on the relaxation obtained in high K solution. The concentration-response curve was shifted to the right in a parallel manner, compatible with competitive inhibition only by the H2-antagonist, cimetidine. Phentolamine and especially propranolol depressed the Em, suggesting antagonism by nonspecific mechanisms. Methysergide and sulpiride induced no significant change in Em, but slightly displaced the curve in a non-parallel manner. Yohimbine had no effect on the relaxation. Clonidine evidently relaxes rabbit cerebral arteries in vitro, even at low, therapeutic concentrations, possibly by acting on H2-histaminergic receptors.This publication has 17 references indexed in Scilit:
- Reversal of clonidine-induced hypotension by β-adrenoceptor blocking drugsEuropean Journal of Pharmacology, 1980
- Asymmetry of the contractile response of the rabbit ear artery to exogenous aminesAmerican Journal of Physiology-Heart and Circulatory Physiology, 1980
- 5-HYDROXYTRYPTAMINE RECEPTORS - CONTRACTILE ACTIVITY AND MODE OF INHIBITION BY METHYSERGIDE IN MAMMALIAN INTRA-CRANICAL AND EXTRA-CRANIAL VESSELS1980
- The dilating effect of histamine on pial arteries of cats and its mediation by H2 receptors.Circulation Research, 1979
- Responses of Small Rabbit Pial Arteries in vitroJournal of Vascular Research, 1979
- Further evidence for central histamine H2-receptor involvement in the hypotensive effect of clonidine in the ratEuropean Journal of Pharmacology, 1977
- No evidence for central histamine-receptor involvement with the hypotensive effect of clonidine in catsEuropean Journal of Pharmacology, 1976
- PHARMACOLOGICAL CHARACTERIZATION OF ADRENERGIC-RECEPTORS OF A RABBIT CEREBRAL-ARTERY INVITRO1976
- Cardiovascular effects of 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (ST 115)European Journal of Pharmacology, 1968
- Evidence for a central hypotensive mechanism of 2-(2,6-dichlorophenylamino)-2-imidazoline (catapresan, ST-155)European Journal of Pharmacology, 1968