ALTERED PERIPHERAL VASODILATOR PROFILE OF NITROGLYCERIN DURING LONG-TERM INFUSION OF N-ACETYLCYSTEINE

Objectives. The aim of this study was to compare the short- and long-t erm effects of intravenous nitroglycerin plus placebo and nitroglyceri n plus N-acetylcysteine on peripheral arteries, veins and microcircula tion in humans. Background. The thiol donor N-acetylcysteine may poten tiate the hemodynamic response to nitrates in nitrate-tolerant and non tolerant patients. The vascular changes responsible for this effect ar e not clear. Methods. Eight male volunteers were treated with nitrogly cerin (0.1 mug/kg per min) combined with N-acetylcysteine (2 g intrave nously, followed by 5 mg/kg per h) or placebo for 23 h in a double-bli nd, randomized, crossover study. Venous volume, the diameter of the ra dial and temporal arteries, calf blood flow and subcutaneous blood flo w were measured at baseline and repeated after 1 and 23 h of infusion. Results. Prolonged coadministration of N-acetylcysteine and nitroglyc erin potentiated the acute venodilator effect of nitroglycerin as esti mated by changes in venous volume (nitroglycerin plus N-acetylcysteine , 4.45 +/- 0.36 ml/100 g; nitroglycerin plus placebo, 3.65 +/- 0.46 ml /100 g, mean +/- SEM, p < 0.05) and prevented development of tolerance as seen after 23 h of treatment with nitroglycerin plus placebo (4.35 +/- 0.25 vs. 3.47 +/- 0.41 ml/100 g, p < 0.05). N-acetylcysteine had no effect on nitroglycerin-induced changes in arterial diameters (p > 0.05) but significantly increased microcirculatory subcutaneous blood flow after 1 h (nitroglycerin plus N-acetylcysteine: 6.3 +/- 1.3 ml/10 0 g per min vs. nitroglycerin plus placebo: 3.5 +/- 0.3 ml/100 g per m in, p < 0.05) and after 23 h (4.4 +/- 0.6 vs. 3.1 +/- 0.5 ml/100 g per min, p < 0.05). Conclusions. The results suggest that coadministratio n of nitroglycerin and N-acetylcysteine in humans 1) potentiates and p reserves nitroglycerin-induced venodilation and 2) augments the effect of nitroglycerin on small resistance vessels (regulating subcutaneous blood flow) without affecting the response to nitroglycerin in middle -sized arteries. Both the development of nitrate tolerance and the adm inistration of N-acetylcysteine significantly change the normal vasodi lator profile of nitroglycerin in humans.