Cardiovascular effects of perfusion of the rostral rat hypothalamus with clonidine: differential interactions with prazosin and yohimbine.
The present studies examined the role of alpha 1- versus alpha 2-adrenoceptors in the cardiovascular effects of clonidine administered into the anterior hypothalamic/pre-optic (AH/PO) region of the forebrain by the push-pull perfusion technique. Push-pull cannulas were placed bilaterally into the AH/PO region of anesthetized, paralyzed and ventilated rats. Perfusion of this area with artificial CSF (0.015 ml/min), yohimbine (5 or 50 microM) for 30 min did not affect mean arterial blood pressure or heart rate. Perfusion of the AH/PO region with clonidine (0.55-5.50 mM) resulted in a concentration-dependent reduction of mean arterial pressure and heart rate. The hypotensive effects of clonidine were found to be greater than the bradycardic effects, when expressed as a percent of pre-infusion baseline values. Co-perfusion with yohimbine (5, 50 microM) significantly attenuated the hypotensive, but not the bradycardic, effects of a single concentration (1.75 mM) of clonidine; this selective antagonism of the hypotensive effect of clonidine by yohimbine was concentration dependent. In contrast to yohimbine, co-perfusion with 5 microM prazosin did not significantly affect either the clonidine-induced hypotension or bradycardia. Co-perfusion with the higher concentration (50 microM) of prazosin significantly reversed the bradycardic, but not the hypotensive, effects of 1.75 mM clonidine. These results suggest that AH/PO clonidine perfusion depresses both mean arterial pressure and heart rate, and that the clonidine-induced hypotension is due to alpha 2-adrenoceptor activation, while the clonidine-induced bradycardia is due to alpha 1-adrenoceptor activation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology*
D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin