Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep.
Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate in many species, but the mechanisms involved are unclear. We investigated whether cortisol-induced renal vasodilatation in conscious sheep depends on interactions with prostaglandins or angiotensin II. Intravenous infusion of cortisol (5 mg/h) for 5 h increased renal conductance (RC) by 1.06 +/- 0.24 ml. min-1. mmHg-1 more than vehicle. During intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1), the cortisol-induced increase in RC (0.28 +/- 0.21 ml. min-1. mmHg-1) was significantly reduced. The cortisol-induced rise in RBF (103 +/- 17 ml/min) was not significantly reduced by indomethacin treatment (76 +/- 9 ml/min). Combined intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1) with Nomega-nitro-L-arginine (2.0 mg. kg-1. h-1), a nitric oxide synthase inhibitor, abolished the cortisol-induced increases in both RC and RBF. Inhibition of angiotensin II synthesis with intravenous captopril (40 mg/h) blocked the renal vasoconstrictor action of angiotensin I but did not inhibit the cortisol-induced increases in RBF and RC. This study provides evidence that nitric oxide and prostaglandins play a role in cortisol-induced renal vasodilatation but indicates that this response is independent of an interaction with angiotensin.
de Matteo
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Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville 3052, Australia.
May
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012077:Renal Artery; D012079:Renal Circulation / Q000187:drug effects*; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D002216:Captopril; D019001:Nitric Oxide Synthase; D006854:Hydrocortisone; D009638:Norepinephrine; D007213:Indomethacin