Relaxation of rabbit cerebral arteries in vitro by clonidine. Evidence of H2-receptor mediation.

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-1) 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-1 papaverine, the Em was 79 +/- 3.9% (mean +/- SEM) and 63.7 +/- 2.4% respectively, and the EC 50 (4.3 +/- 2.0) 10(-8) mol.l-1 and (1.3 +/- 1.0) 10(-8) mol.l-1 respectively. The action of 6 specific antagonists at 3.10(-6) mol.l-1 was tested on the relaxation obtained in high potassium 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 non-specific mechanisms. Methysergide and sulpiride induced no significant change in Em, but slightly displaced the curve in a nonparallel manner. Yohimbine had no effect on the relaxation. These results are interpreted as indicating that clonidine relaxes rabbit cerebral arteries in vitro, even at low, therapeutic concentrations, possibly by acting on H2-histaminergic receptors.