Ka. Munger et al., MAINTENANCE OF ENDOTHELIN-INDUCED RENAL ARTERIOLAR CONSTRICTION IN RATS IS CYCLOOXYGENASE DEPENDENT, The American journal of physiology, 264(4), 1993, pp. 637-644
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.