Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

Philipp A. Kaufmann, Ornella E. Rimoldi, Tomaso Gnecchi-Ruscone, Thomas F. Luscher, Paolo G. Camici

Research output: Contribution to journalArticle

Abstract

We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N G-monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in recently transplanted denervated hearts. At baseline, myocardial blood flow (MBF; ml·min -1·g -1) was measured at rest and during intravenous administration of adenosine (140 μg·kg -1·min -1) in 10 controls (47 ± 5 yr) and 10 CAD patients (58 ± 8 yr; P <0.01 vs. controls) using positron emission tomography and 15O-labeled water. Both MBF measurements were repeated during intravenous infusion of 10 mg/kg L-NMMA. CFR was calculated as the ratio of MBF during adenosine to MBF at rest. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00 ± 1.10 to 6.15 ± 1.35; P <0.0001) and in patients, both in territories subtended by stenotic coronary arteries (>70% luminal diameter; 2.06 ± 1.13 to 3.21 ± 1.07; P <0.01) and in remote segments (3.20 ± 1.23 to 3.92 ± 1.62; P <0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by a mechanism that can be relieved by systemic NOS inhibition with L-NMMA.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Autonomic nervous system
  • Cardiac imaging
  • Coronary circulation
  • Ischemic heart disease
  • Positron emission tomography

ASJC Scopus subject areas

  • Physiology

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