Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide.
Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate, but the mechanisms are unclear. We investigated whether the cortisol-induced increment in RBF is a direct renal action or secondary to its systemic effects and whether nitric oxide (NO) plays a role in this response. In conscious sheep, cortisol infused intravenously (5.0 mg/h) or into the renal artery (1.3 mg/h) for 5 h increased RBF by 66 +/- 8 and 53 +/- 11 ml/min, respectively. Plasma glucose was increased by intravenous cortisol (0.4 +/- 0.1 mmol/l) but not by intrarenal cortisol. Renal vein plasma cortisol levels were similar at the end of each infusion (193 +/- 31 intravenously; 151 +/- 25 nmol/l intrarenal), but systemic levels were different (277 +/- 31 intravenous; 69 +/- 10 nmol/l intrarenal). Inhibition of NO synthesis by N omega-nitro-L-arginine infused intravenously (10 mg/kg followed by 5 mg.kg-1.h-1) or intrarenally (2 mg.kg-1.h-1) significantly reduced the cortisol-induced renal vasodilatation. In contrast, constriction of the renal vasculature with intrarenal angiotensin (0.3 microgram/h) did not prevent the cortisol-induced renal vasodilatation. These findings demonstrate that cortisol acts directly on the kidney to cause renal vasodilatation and to increase RBF and suggest that this response involves the endothelium-derived relaxing factor NO.
De Matteo
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Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Australia.
May
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D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D011188:Potassium / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012082:Renal Veins / Q000502:physiology; D012756:Sheep; D012964:Sodium / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D019335:Nitroarginine; D009569:Nitric Oxide; D012964:Sodium; D011188:Potassium; D006854:Hydrocortisone