NITRIC-OXIDE ACTIVITY IN THE HUMAN CORONARY CIRCULATION - IMPACT OF RISK-FACTORS FOR CORONARY ATHEROSCLEROSIS

The bioavailability of nitric oxide (NO) in the human coronary circula tion at rest and after acetylcholine (ACH)-induced vasodilation was in vestigated in 32 patients with angiographically normal coronary arteri es, The effects of intracoronary L-N-G monomethyl arginine (L-NMMA) we re investigated at rest and after AGH, sodium nitroprusside, and adeno sine, L-NMMA (64 mu mol/min) increased resting coronary vascular resis tance by 22% (P<0.001), reduced distal epicardial coronary artery diam eter by 12.6% (P<0.001), and inhibited AGH-induced coronary epicardial and microvascular vasodilation. These effects were reversed with intr acoronary L-arginine. L-NMMA did not inhibit dilation in response to s odium nitroprusside and adenosine, 23 patients were exposed to one or more coronary risk factors, The vasoconstrictor effect of L-NMMA on th e epicardial and microvessels was greater in patients free of risk fac tors: Coronary vascular resistance was 36% higher in patients without risks, compared to 17% higher in patients with risks (P<0.05), Both ep icardial and microvascular dilator effects of ACH were greater in pati ents without risk factors, and the inhibition of these effects by L-NM MA was also greater in patients without risk factors, Thus: (a) NO con tributes importantly to resting epicardial and coronary microvascular tone, (b) coronary vascular dilation in response to ACH is predominant ly due to increased production of NO, and (c) despite the absence of a ngiographic evidence of atherosclerosis, exposure to coronary risk fac tors is associated with reduced resting and stimulated bioavailability of NO from the human coronary circulation.