ROLE OF ENDOTHELIN AND PROSTAGLANDINS IN RADIOCONTRAST-INDUCED RENAL-ARTERY CONSTRICTION

Infusion of radiocontrast agents in vivo results in renal artery const riction and subsequent renal hypoperfusion. To examine the role of end othelin and of prostaglandins in radiocontrast-mediated renal vasocons triction, rats were treated with an endothelin receptor antagonist, CP 170687, and with indomethacin. The dose of CP170687 utilized was suffi cient to reverse endothelin1-mediated constriction of isolated aortic rings and of renal blood flow in intact rats. In normal rats there was a transient drop in renal blood flow to 80% of baseline following sod ium iothalamate injection, an effect which was not prevented by CP1706 87. In rats first given indomethacin, the drop in renal blood flow was more pronounced (to 63% of baseline) and was sustained. In this insta nce, CP170687 fully reversed the sustained decrease of renal perfusion . CP170687 also diminished the rise in systemic blood pressure seen fo llowing iothalamate injection. In the absence of indomethacin, iothala mate increased urinary prostaglandin E2 to a maximum of sevenfold abov e baseline values. In summary, injection of radiocontrast results in a n immediate decrease in renal blood flow that is counteracted by an in crease in renal prostaglandin formation. When prostaglandin synthesis is inhibited, prolonged endothelin-mediated renal vasoconstriction is observed that is reversed by an endothelin receptor antagonist.