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  • Title: Analysis of adrenoceptor blockade and hypotension elicited by urapidil and prazosin in conscious rat.
    Author: Goering J, Zimmerman BG.
    Journal: J Pharmacol Exp Ther; 1986 May; 237(2):553-7. PubMed ID: 2871176.
    Abstract:
    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.
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