INTRARENAL PROSTAGLANDIN RELEASE ATTENUATES THE RENAL VASOCONSTRICTOR ACTIVITY OF ANGIOTENSIN

Abstract

In anesthetized dogs, infusions of angiotensin II into the renal artery caused dosedependent decreases in renal blood flow and release of a prostaglandin E2-like substance into the renal venous blood. Inhibitors of prostaglandin synthesis, indomethacin (0.1-2 mg/kg i.v.) or meclofenamate (1 mg/kg iv.) reduced renal blood flow and urine output but did not substantially affect blood pressure or hindlimb blood flow. After indomethacin or meclofenamate, angiotensin II no longer caused release of prostaglandin E2-like material from kidney and the renal vasoconstrictor action of angiotensin II was augmented. Enhancement of the renal vascular effects of angiotensin II was greatest with low infusion rates of the octapeptide (3-20 ng/kg/min i.a.). Reductions in hindlimb blood flow produced by i.a. infusions of angiotensin II were not accompanied by prostaglandin release and the responses were not augmented by indomethacin. Indomethacin enhanced the renal (but not hindlimb) vasoconstrictor effects of norepinephrine. The results support the hypothesis that intrarenal prostaglandin E2 generation in response to angiotensin II attenuates the increase in renal vascular resistance produced by angiotensin.