HEMODYNAMIC-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 N O synthase inhibitor) and L-arginine (a NO synthase substrate) on haem odynamics in healthy men at rest and during exercise. Methods We infus ed L-NMMA and saline placebo intravenously in two groups of eight heal thy men. Each group underwent a two-phase, randomized, single-blind cr ossover 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 pe rformed before, during and after a 12 min stepped exercise protocol st arting 6 min after the intravenous infusion. A further six men receive d, according to the same study design, 30 g L-arginine over 30 min and saline placebo before exercise. Blood pressure was measured by sphygm omanometry 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 wi th 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 compa rison) than after infusion of saline placebo. During exercise there wa s no significant difference between total SVRI after infusions of L-NM MA 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 haemody namics in men at rest during exercise and during recovery. Conclusions Effects of L-NMMA on total systemic vascular resistance during exerci se are less marked than are those on subjects at rest probably because vasodilatation of resistance vessels of skeletal muscle during exerci se is mediated mainly by factors other than NO. Our results also sugge st that NO synthesis in healthy men is not substrate limited either at rest or during exercise. (C) 1998 Lippincott-Raven Publishers.