Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans

Philipp A. Kaufmann, Ornella Rimoldi, Tomaso Gnecchi-Ruscone, Robert S. Bonser, Thomas F. Lüscher, Paolo G. Camici

Research output: Contribution to journalArticlepeer-review

Abstract

Background-Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. Methods and Results-MBF (mL · min-1 · g-1) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg NG-monomethyl-L- arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n= 13), 10 mg/kg L-NMMA; group 4 (n= 8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P

Original languageEnglish
Pages (from-to)1431-1436
Number of pages6
JournalCirculation
Volume110
Issue number11
DOIs
Publication statusPublished - Sep 14 2004

Keywords

  • Blood flow
  • Imaging
  • Nitric oxide
  • Synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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