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.