Inhibition of nitric oxide synthesis in human epicardial coronary arteriesand stenoses in relation to serum lipid level

Administration of N-G-monomethyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthase, causes a reduction in epicardial coronary artery and steno sis diameter in patients with coronary artery disease, indicating that thes e diseased vessels produce nitric oxide. Elevations of low density lipoprot ein cholesterol impair human endothelium-dependent relaxation. The relation ship between serum lipid level and nitric oxide production by normal and at heromatous human epicardial coronary arteries in vivo is unknown. The effec ts of an intracoronary infusion of LNMMA (8 and 16 mu mol/min) followed by intracoronary administration of 250 meg nitroglycerin on non-stenotic proxi mal and distal coronary segments and coronary stenoses were studied in 11 p atients with coronary artery disease and in 19 patients with 'normal arteri ograms'. Coronary luminal diameter was measured by computerized quantitativ e angiography. In patients viith cholesterol level greater than or equal to 220 mg/dl, no significant response to LNMMA was observed in the proximal s egments in either those with 'normal angiograms' or those with coronary dis ease. In patients with cholesterol < 220 mg/dl significant constriction (P < 0.01) was observed in the proximal segments of patients with 'normal coro nary angiograms' at both 8 and 16 mu mol doses, but occurred only at the 16 mu mol/min dose (P < 0.01) in those with coronary disease. In conclusion t he difference in vasomotor response to LNMMA in relation to cholesterol lev el is localised to the proximal coronary segments, and the response does no t correlate with cholesterol or triglyceride level. This is therefore more likely to be an indirect effect of elevated cholesterol, e.g. undetected at heroma, than a direct effect on nitric oxide synthesis. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.