Effects of Inhibition of Nitric Oxide Synthase on Muscular Arteries During Exercise: Nitric Oxide Does Not Contribute to Vasodilation During Exercise or in Recovery

J Am Heart Assoc. 2020 Aug 18;9(16):e013849. doi: 10.1161/JAHA.119.013849. Epub 2020 Aug 12.

Abstract

Background Basal release of nitric oxide (NO) from the vascular endothelium regulates the tone of muscular arteries and resistance vasculature. Effects of NO on muscular arteries could be particularly important during exercise when shear stress may stimulate increased NO synthesis. Methods and Results We investigated acute effects of NO synthase inhibition on exercise hemodynamics using NG-monomethyl-l-arginine (l-NMMA), a nonselective NO synthase -inhibitor. Healthy volunteers (n=10, 5 female, 19-33 years) participated in a 2-phase randomized crossover study, receiving l-NMMA (6 mg/kg, iv over 5 minutes) or placebo before bicycle exercise (25-150 W for 12 minutes). Blood pressure, cardiac output (measured by dilution of soluble and inert tracers) and femoral artery diameter were measured before, during, and after exercise. At rest, l-NMMA reduced heart rate (by 16.2±4.3 bpm relative to placebo, P<0.01), increased peripheral vascular resistance (by 7.0±1.4 mmHg per L/min, P<0.001), mean arterial blood pressure (by 8.9±3.5 mmHg, P<0.05), and blunted an increase in femoral artery diameter that occurred immediately before exercise (change in diameter: 0.14±0.04 versus 0.32±0.06 mm after l-NMMA and placebo, P<0.01). During/after exercise l-NMMA had no significant effect on peripheral resistance, cardiac output, or on femoral artery diameter. Conclusions These results suggest that NO plays little role in modulating muscular artery function during exercise but that it may mediate changes in muscular artery tone immediately before exercise.

Keywords: exercise physiology; nitric oxide; nitric oxide synthase.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arterial Pressure / drug effects
  • Arterial Pressure / physiology
  • Arteries / enzymology*
  • Arteries / physiology
  • Cardiac Output / drug effects
  • Cross-Over Studies
  • Enzyme Inhibitors / pharmacology
  • Exercise / physiology*
  • Exercise Test
  • Female
  • Femoral Artery / drug effects
  • Femoral Artery / physiology
  • Humans
  • Male
  • Muscle, Skeletal / blood supply*
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Placebos
  • Pulse Wave Analysis / methods
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilation / physiology*
  • Young Adult
  • omega-N-Methylarginine / pharmacology

Substances

  • Enzyme Inhibitors
  • Placebos
  • omega-N-Methylarginine
  • Nitric Oxide
  • Nitric Oxide Synthase