Haemodynamic effects of inhibition of nitric oxide synthase and of L-arginine at rest and during exercise

Objective: To compare effects of N(G)-monomethyl-L-arginine (L-NMMA; a NO synthase inhibitor) and L-arginine (a NO synthase substrate) on haemodynamics in healthy men at rest and during exercise. Methods: We infused L-NMMA and saline placebo intravenously in two groups of eight healthy men. Each group underwent a two-phase, randomized, single-blind crossover study. Men in one group received 3 mg/kg L-NMMA and men in the other group received 6 mg/kg L-NMMA. Haemodynamic measurements were performed before, during and after a 12 min stepped exercise protocol starting 6 min after the intravenous infusion. A further six men received, according to the same study design, 30 g L-arginine over 30 min and saline placebo before exercise. Blood pressure was measured by sphygmomanometry and cardiac output by bioimpedance, allowing computation of total systemic vascular resistance index (SVRI). Results: Infusion of 6 mg/kg L-NMMA into men at rest produced modest increases (compared with effect of saline placebo) in systolic and diastolic blood pressures of 4.1 ± 1.1 and 12.6 ± 3.5%, respectively (means ± SEM, P < 0.01 for both comparisons) and a marked increase in SVRI of 39.2 ± 5.2% (P < 0.01). Cardiac index and heart rate were 22.0 ± 3.3 and 17.0 ± 4.4% lower after administration of L-NMMA (P < 0.01 for each comparison) than after infusion of saline placebo. During exercise there was no significant difference between total SVRI after infusions of L-NMMA and saline (difference not significant, diminished with increasing exercise). Six minutes into recovery the difference between total SVRI after infusions of L-NMMA and saline reappeared with SVRI 25 ± 6.9% higher after infusion of L-NMMA than after infusion of saline (P < 0.01). Administration of L-arginine had no significant effect on haemodynamics in men at rest, during exercise and during recovery. Conclusions: Effects of L-NMMA on total systemic vascular resistance during exercise are less marked than are those on subjects at rest, probably because vasodilatation of resistance vessels of skeletal muscle during exercise is mediated mainly by factors other than NO. Our results also suggest that NO synthesis in healthy men is not substrate limited either at rest or during exercise.