Influence of the renin-angiotensin system on the effect of prostaglandin synthesis inhibitors in the renal vasculature.
The effect of meclofenamate and indomethacin on renal blood flow and renal vascular resistance was determined under basal experimental conditions and during renal ischemia in pentobarbital-anesthetized dogs. Renal blood flow was measured with an electromagnetic flowmeter and renal arterial pressure was recorded from a catheter in the renal artery. Intra-arterial infusion of indomethacin or meclofenamate in concentrations of 4 and 4 to 8 mu-g/ml, respectively, did not cause any significant change in renal blood flow or renal vascular resistance under basal conditions. During the period of ischemia (50% reduction in renal blood flow), 4 mu-g/ml of either prostaglandin synthetase inhibitor caused a marked increase in renal vascular resistance. Prostaglandin E in the renal venous blood was decreased at the time renal vascular resistance was increased by meclofenamate. The renal vasoconstrictor response to angiotensin II injected intravenously was potentiated by both inhibitors under basal as well as ischemic conditions, which also suggested that prostaglandin synthesis was inhibited. The angiotensin antagonist 1-sar-8-ala-angiotensin II was infused intra-arterially in concentrations of 20 and 40 mmu-g/ml during renal ischemia. Subsequent administration of meclofenamate increased renal vascular resistance only slightly. The results of these experiments indicated that renal prostaglandins have more influence on renal blood flow during renal ischemia than under basal conditions, and that the renin-angiotensin system may be involved in activating synthesis and release of prostaglandins during ischemia.
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D011458:Prostaglandins E / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D012078:Renal Artery Obstruction / Q000503:physiopathology; D012083:Renin / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D000804:Angiotensin II; D006899:Mixed Function Oxygenases; D012083:Renin; D007213:Indomethacin