Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries.
Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to -21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Dubois-Randé
J L
JL
Department of Cardiology and Physiology (Unité d'hémodynamique et de cardiologie interventionnelle, service d'explorations fonctionnelles, INSERM U2 and U 296), Hôpital Henri Mondor, Creteil, France.
Zelinsky
R
R
Roudot
F
F
Chabrier
P E
PE
Castaigne
A
A
Geschwind
H
H
Adnot
S
S
D000109:Acetylcholine / Q000494:pharmacology*; D000368:Aged; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D001783:Blood Flow Velocity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine