Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat.
The angiotensin antagonist, saralasin, (10 and 30 mg/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 less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) 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. Propranolol (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 less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 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 AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.
D000818:Animals; D016861:Cyclooxygenase Inhibitors; D007668:Kidney / Q000502:physiology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism / Q000652:urine; D051381:Rats; D012083:Renin / Q000378:metabolism*; D012504:Saralasin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D008469:Meclofenamic Acid; D011433:Propranolol; D012083:Renin; D012504:Saralasin