Effects of clonidine on alpha-adrenoceptors in the autoperfused hindquarters of the pithed rat.
The effects of clonidine were assessed in pithed rats on responses to spinal cord stimulation of heart rate (HR), systemic blood pressure (BP) and perfusion pressure (PP) in the autoperfused hindquarters. Graded increases in HR, BP and PP were elicited by 10 s periods of spinal stimulation at frequencies of 1, 3 and 10 Hz; the vasoconstrictor responses (BP and PP) were biphasic. Clonidine (3-100 micrograms/kg) caused dose-dependent reductions of HR responses and of the first phase of BP and PP responses to spinal stimulation; the reductions were to a lesser extent with increasing frequency of stimulation. Responses to exogenous noradrenaline were unaffected by clonidine. In contrast, the second phase of the vasoconstrictor responses to 10 Hz stimulation was enhanced by clonidine (3-30 micrograms/kg): this phase of the responses is probably mediated by adrenal catecholamines. Clonidine itself (10-100 micrograms/kg) increased resting levels of BP and PP but not HR. The direct effects of clonidine as well as the effects on responses to spinal stimulation were blocked by phentolamine (1 mg/kg). The results indicate that clonidine selectively activates prejunctional alpha-adrenoceptors in the rat heart and hindquarters in vivo. The results also indicate that clonidine may potentiate the release of adrenal catecholamines, and it is suggested that it may do so by acting as an antagonist at inhibitory alpha-adrenoceptors in the adrenal medulla.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D014403:Tubocurarine; D009638:Norepinephrine; D010646:Phentolamine