Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses.
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.
Medical Research Council Clinical Sciences Center, Imperial College, Hammersmith Hospital, London, United Kingdom.
Philipp A
PA
Kaufmann
Ornella E
OE
Rimoldi
Tomaso
T
Gnecchi-Ruscone
Thomas F
TF
Luscher
Paolo G
PG
Camici
D000241:Adenosine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049268:Positron-Emission Tomography; D012107:Research Design; D012720:Severity of Illness Index; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D000241:Adenosine