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Analysis of adrenoceptor blockade and hypotension elicited by urapidil and prazosin in conscious rat

J Goering and BG Zimmerman

The adrenoceptor blocking properties and hypotensive effects of the alpha-1 blocking agents urapidil and prazosin were compared in conscious instrumented rats. Both urapidil and prazosin in i.v. doses of 3 and 6 mg/kg and 0.125 and 0.25 mg/kg, respectively, blocked the pressor response to the alpha-1 adrenoceptor agonist phenylephrine. The hypotensive effects of urapidil and prazosin in these doses were equivalent. Mechanisms of the blood pressure compensation to urapidil- induced hypotension were examined with the arginine vasopressin (AVP) antagonist, d(CH2)5Tyr(Me)AVP, and the angiotensin converting enzyme inhibitor, MK-422. Urapidil alone (6 mg/kg i.v.) and after the AVP antagonist caused a similar degree of hypotension (22 and 15% decrease, respectively, in mean blood pressure). When the alpha-1 antagonist was administered after converting enzyme inhibition, it caused a significantly greater decrease in blood pressure (37%) than in the previous two groups, but not different from that obtained after combined AVP antagonism and converting enzyme inhibition (30% decrease). These results indicate that the renin-angiotensin system compensates for the hypotensive effect due to alpha-1 adrenoceptor blockade, whereas AVP, even assuming that the circulating level was increased by urapidil, was without effect on blood pressure.

Volume 237, Issue 2, pp. 553-557, 05/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.