Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans

J Am Coll Cardiol. 2000 Jul;36(1):213-8. doi: 10.1016/s0735-1097(00)00674-4.


Objectives: We sought to investigate baroreceptor regulation of sympathetic nerve activity and hemodynamics after inhibition of nitric oxide (NO) synthesis.

Background: Both the sympathetic nervous system and endothelium-derived substances play essential roles in cardiovascular homeostasis and diseases. Little is known about their interactions.

Methods: In healthy volunteers, we recorded muscle sympathetic nerve activity (MSA) with microneurography and central hemodynamics measured at different levels of central venous pressure induced by lower body negative pressure.

Results: After administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from 53 to 38 mL/min/m2 (p < 0.002). Administration of L-NMMA prevented the compensatory increase of heart rate, but not MSA, to orthostatic stress. The altered response of heart rate was not due to higher blood pressure, because heart rate responses were not altered during infusion of the alpha-1-adrenoceptor agonist phenylephrine (titrated to an equal increase of systolic blood pressure). In the presence of equal systolic blood pressure and central venous pressure, we found no difference in MSA during phenylephrine and L-NMMA infusion.

Conclusions: This study demonstrates a highly specific alteration of baroreceptor regulation of heart rate but not muscle sympathetic activity after inhibition of NO synthesis in healthy volunteers. This suggests an important role of NO in reflex-mediated heart rate regulation in humans.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adult
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Humans
  • Infusions, Intravenous
  • Lower Body Negative Pressure
  • Male
  • Muscle, Skeletal / innervation
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Phenylephrine / pharmacology
  • Pressoreceptors / drug effects
  • Pressoreceptors / physiopathology*
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Reference Values
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiopathology*
  • omega-N-Methylarginine / pharmacology


  • Adrenergic alpha-Agonists
  • Enzyme Inhibitors
  • Receptors, Adrenergic, alpha-1
  • Phenylephrine
  • omega-N-Methylarginine
  • Nitric Oxide Synthase