Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep

Abstract

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−1more 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 N ω-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.