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.