SARALASIN-INDUCED RENIN RELEASE - ITS BLOCKADE BY PROSTAGLANDIN SYNTHESIS INHIBITORS IN THE CONSCIOUS RAT

被引:28
作者
CAMPBELL, WB
JACKSON, EK
GRAHAM, RM
机构
[1] University of Texas Health Science Center, Department of Pharmacology, Division of Clinical Pharmacology, Dallas, TX
关键词
Arachidonic acid; Indomethacin; Meclofenamate; Propranolol; Prostaglandin E; Serum renin activity; Sodium depletion;
D O I
10.1161/01.HYP.1.6.637
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The angiotensin antagonist, saralasin, (10 and 30 rag/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 ± 0.4 to 16.2 ± 3.7 and 22.5 ± 2.4 ng/ml/hr (p < 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E1(PGE1) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Prorjranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p < 0.001). In sodium-depleted rats, saralasin (03 mg/kg) increased SRA from 12 ± 2 to 119 ± 6 ng/ml/hr (p < 0.001) and decreased blood pressure by 6% (p < 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE, by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling All-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor. © 1979 American Heart Association, Inc.
引用
收藏
页码:637 / 642
页数:6
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