ObjectiveThe present study investigated whether the nitric oxide (NO) system is involved in cyclosporin A (CsA)-induced changes in cardiovascular and renal function in man.Subjects and methodsTen healthy volunteers were investigated twice - with and without intake of a single dose of CsA (8 mg/kg). NG-monomethyl-L-arginine (L-NMMA; 3 mg/kg) was injected 4 h after study start on each day.ResultsThere 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 F1α(6-keto-PgF1α) and thromboxane B2(TxB2) when compsbared to the control day. The urinary excretion rate of NOxand cGMP declined gradually on the control day. In contrast, there was a minor, non-significant increase in NOxand cGMP excretion after CsA, followed by a decrease (29 ± 2 and 16 ± 4%, respectively) after L-NMMA in parallel with the decrease in GFR.ConclusionThe 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.