Analysis of adrenoceptor blockade and hypotension elicited by urapidil and prazosin in conscious rat.
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.
Goering
J
J
Zimmerman
B G
BG
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D010879:Piperazines; D001127:Arginine Vasopressin; D010656:Phenylephrine; D004656:Enalapril; C015568:urapidil; D015773:Enalaprilat; D011224:Prazosin