ACUTE EFFECTS OF INCREASING DOSES OF NICORANDIL ON RENAL-FUNCTION IN MAN

The effects of nicorandil, a nicotinamide derived vasodilator combinin g nitrate and potassium channel opener actions, on kidney function hav e not been determined. This study investigated changes in renal blood flow and glomerular filtration rate as estimated using simultaneous I- 131-iodohippurate and I-125-iothalamate plasma clearances. Forty-two h ealthy subjects in sodium balance received placebo and 2.5 mg (n = 8), 5 mg (n = 9), 10 mg (n = 8), 20 mg (n = 8) or 30 mg (n = 9) nicorandi l orally. Peak nicorandil plasma concentrations occurred in the first hour. Nicorandil produced dose related decreases in blood pressure wit h maximum reductions (mean +/- standard error of the mean) after 30 mg of -6 +/- 1 mmHg systolic and -8 +/- 2 mmHg diastolic. Renal blood fl ow averaged 655 +/- 28 ml/minute/1.73 m2 after placebo. Renal blood fl ow changed 10 +/- 11% after 2.5 mg, -6 +/- 8% after 5 mg, -12 +/- 11% after 10 mg, -11 +/- 5% after 20 mg, and 8 +/- 6% after 30 mg, however , these changes did not reach statistical significance. Glomerular fil tration rate averaged 113 +/- 3 ml/minute/1.73 m2 and was unaltered af ter nicorandil. Nicorandil had no effect on filtration fraction but fr actional excretion of sodium tended to decrease with dose. These dose- related effects of nicorandil are consistent with other mixed vasodila tors. At therapeutic doses, renal perfusion and function are preserved despite reductions in systemic blood pressure by nicorandil.