Inhibition of nitric oxide synthesis in human epicardial coronary arteries and 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 stenosis diameter in patients with coronary artery disease, indicating that these diseased vessels produce nitric oxide. Elevations of low density lipoprotein cholesterol impair human endothelium-dependent relaxation. The relationship between serum lipid level and nitric oxide production by normal and atheromatous human epicardial coronary arteries in vivo is unknown. The effects of an intracoronary infusion of LNMMA (8 and 16 micromol/min) followed by intracoronary administration of 250 mcg nitroglycerin on non-stenotic proximal and distal coronary segments and coronary stenoses were studied in 11 patients with coronary artery disease and in 19 patients with 'normal arteriograms'. Coronary luminal diameter was measured by computerized quantitative angiography. In patients with cholesterol level> or = 220 mg/dl, no significant response to LNMMA was observed in the proximal segments in either those with 'normal angiograms' or those with coronary disease. In patients with cholesterol <220 mg/dl significant constriction (P<0.01) was observed in the proximal segments of patients with 'normal coronary angiograms' at both 8 and 16 micromol doses, but occurred only at the 16 micromol/min dose (P<0.01) in those with coronary disease. In conclusion the difference in vasomotor response to LNMMA in relation to cholesterol level is localised to the proximal coronary segments, and the response does not correlate with cholesterol or triglyceride level. This is therefore more likely to be an indirect effect of elevated cholesterol, e.g. undetected atheroma, than a direct effect on nitric oxide synthesis.
Tentolouris
C
C
Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece.
Tousoulis
D
D
Crake
T
T
Katsimaglis
G
G
Stefanadis
C
C
Davies
G
G
Toutouzas
P
P
D000328:Adult; D000787:Angina Pectoris / Q000175:diagnosis / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood*; D017023:Coronary Angiography / Q000379:methods; D003327:Coronary Disease / Q000175:diagnosis / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005080:Exercise Test / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014280:Triglycerides / Q000097:blood; D014654:Vascular Patency / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014280:Triglycerides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase