MAINTENANCE OF ENDOTHELIN-INDUCED RENAL ARTERIOLAR CONSTRICTION IN RATS IS CYCLOOXYGENASE DEPENDENT

Influence of arachidonate cyclooxygenase (COX) products on endothelin (ET)-evoked renal vasoconstriction was assessed. In microperfused rat afferent (AA) and efferent arterioles (EA), indomethacin had no effect s on the maximal contraction of both AA and EA by ET, but reduced the duration of ET-induced constriction in both arterioles. ET infusion to rats in vivo resulted in a selective increase in efferent but not aff erent arteriolar resistance, leading to a dramatic increase in transca pillary hydraulic pressure difference. Glomerular filtration rate (GFR ), which fell progressively during infusion of ET alone, was markedly preserved by COX inhibition. but not during selective thromboxane A2 a ntagonism. In isolated glomeruli, release of prostaglandin (PG) F2alph a in response to 10(-6) mol/l ET exceeded that of PGE2 by a ratio of 3 :2. Collectively, these data provide strong evidence that locally rele ased COX products, possibly PGF2alpha, play a key role in sustaining E T-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without aff ecting EA constriction in vivo, thereby resulting in a dramatic revers al of the effects of ET on GFR.