Document Detail

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses.
MedLine Citation:
PMID:  17660388     Owner:  NLM     Status:  MEDLINE    
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 x min(-1) x g(-1)) was measured at rest and during intravenous administration of adenosine (140 microg x kg(-1) x 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 (15)O-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.
Philipp A Kaufmann; Ornella E Rimoldi; Tomaso Gnecchi-Ruscone; Thomas F Luscher; Paolo G Camici
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-09     Completed Date:  2007-11-21     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2178-82     Citation Subset:  IM    
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MeSH Terms
Adenosine / administration & dosage,  diagnostic use*
Blood Pressure / drug effects
Coronary Stenosis / diagnosis*,  enzymology,  physiopathology
Coronary Vessels / drug effects*,  physiopathology,  radionuclide imaging
Enzyme Inhibitors / administration & dosage,  pharmacology*
Fractional Flow Reserve, Myocardial / drug effects*
Heart Rate / drug effects
Hyperemia / enzymology,  physiopathology,  radionuclide imaging
Infusions, Intravenous
Middle Aged
Nitric Oxide Synthase / antagonists & inhibitors*,  metabolism
Positron-Emission Tomography
Research Design
Severity of Illness Index
Vasodilation / drug effects*
Vasodilator Agents / administration & dosage,  diagnostic use*
omega-N-Methylarginine / administration & dosage,  pharmacology*
Grant Support
MC_U120084164//Medical Research Council
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Vasodilator Agents; 27JT06E6GR/omega-N-Methylarginine; EC Oxide Synthase; K72T3FS567/Adenosine

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