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 effects 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 afferent arteriolar resistance, leading to a dramatic increase in transcapillary 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 antagonism. In isolated glomeruli, release of prostaglandin (PG) F2 alpha in response to 10(-6) mol/l ET exceeded that the PGE2 by a ratio of 3.2. Collectively, these data provide strong evidence that locally released COX products, possibly PGF2 alpha, play a key role in sustaining ET-induced renal arteriolar constriction. COX inhibition leads to acute vasorelaxation of AA despite continued ET administration, without affecting EA constriction in vivo, thereby resulting in a dramatic reversal of the effects of ET on GFR.
Munger
K A
KA
Department of Medicine, Emory University, Atlanta, Georgia.
Takahashi
K
K
Awazu
M
M
Frazer
M
M
Falk
S A
SA
Conger
J D
JD
Badr
K F
KF
D000818:Animals; D001160:Arterioles / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology / Q000648:ultrastructure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D016232:Endothelins; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin