Effects of nitric oxide blockade and cyclosporin A on cardiovascular and renal function in normal man.

Abstract

The present study investigated whether the nitric oxide (NO) system is involved in cyclosporin A (CsA)-induced changes in cardiovascular and renal function in man. Ten healthy volunteers were investigated twice--with and without intake of a single dose of CsA (8 mg/kg). N(G)-monomethyl-L-arginine (L-NMMA; 3 mg/kg) was injected 4 h after study start on each day. There was no change in glomerular filtration rate (GFR) on the day without CsA. CsA alone did not change GFR, but after L-NMMA injection, GFR decreased significantly from 101 +/- 4 to 91 +/- 4 ml/min. L-NMMA increased renal vascular resistance with no difference between the two study days. CsA increased significantly the diastolic blood pressure (BP) by 8 +/- 2% and the heart rate (HR) by 30 +/- 4%, without changes in cardiac output L-NMMA further increased BP by around 8%, and decreased HR by 11% and cardiac output by 20% on both study days. L-NMMA decreased urinary flow rate by around 25% and renal sodium clearance from 1.1 to approximately 0.6 ml/min on both study days. CsA decreased plasma renin significantly and increased the urinary excretion rate of prostaglandin E2 (PgE2), 6-keto-prostaglandin F1alpha (6-keto-PgF1alpha) and thromboxane B2(TxB2) when compared to the control day. The urinary excretion rate of NOx and cGMP declined gradually on the control day. In contrast, there was a minor, non-significant increase in NOx and cGMP excretion after CsA, followed by a decrease (29 +/- 2 and 16 +/- 4%, respectively) after L-NMMA in parallel with the decrease in GFR. The present findings suggest that NO does not play a major role during acute CsA-induced changes in cardiovascular function and renal haemodynamics in man. Renal NO synthesis, however, may attenuate the acute CsA-induced decrease in GFR.