Cardiovascular effects of central administration of clonidine in conscious cats

The effects on arterial blood pressure and heart rate after an intracerebroventricular (i.c.v.) administration of clonidine were investigated using conscious normotensive cats. Injection of clonidine (5-10 mu g; 5 mu l; i.c.v.) elicited a decrease in mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner. The highest dose of 10 mu g of clonidine decreased MAP and HR by 39 +/- 3 mmHg and 74 +/- 5 b.p.m., respectively (n = 7). Pretreatment with yohimbine, the alpha(2)-adrenoceptor antagonist (8 mu g; 5 mu l; i.c.v.) blocked the cardiovascular responses to a subsequent i.c.v. injection of 10 mu g clonidine (n = 7). Furthermore, preadministration of cimetidine (100 mu g; 5 mu l; i.c.v.), the H-2 histamine receptor antagonist with imidazoline receptor activating properties, prevented the decreases in MAP and HR to a subsequent i.c.v. injection of 10 mu g clonidine (n = 7). By contrast, pretreatment with the specific I-1 imidazoline receptor blocker, efaroxan (100-500 mu g; 5 mu l; i.c.v.), failed to inhibit the cardiovascular effects of an i.c.v. administration of 10 mu g clonidine (n = 7). These results suggest that the effects of centrally administered clonidine on MAP and KR are probably not mediated through activation of the I-1 subtype of imidazoline receptors in conscious cats. However, the cardiovascular effects elicited by i.c.v. administration of clonidine appear to result from stimulation of central alpha(2)-adrenergic or the H-2 histaminergic-like receptors. (C) 1997 Elsevier Science B.V.