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Endothelial Mediation of Coronary Vascular Tone: Nitric Oxide Attenuation of Cholinergic Vasospastic Challenge

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Uniformed Services University Of The Health Sciences Bethesda United States

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The hypothesis tested was that the endothelium modulates the effect of acetylcholine, a vasoconstrictor of porcine coronary arteries, and limits the loss of flow occurring during a cholinergic vasospastic episode. Acetylcholine was injected into a coronary artery in an open-chest swine model before ACh onlyand after infusion of substance P SPACh, an endothelial-dependent vasodilator, and nitroglycerin NTGACh, an endothelial-independent vasodilator in two groups, Control and N-nitro-L-arginine NOLA treated. NOLA is a chemical inhibitor of an endothelium-derived relaxing factor EDRF thought to be nitric oxideNO produced by vascular endothelium. The hemodynamic parameters of mean and phasic coronary artery flows, arterial and intraventricular pressures, dPdt and ECG Lead II were continuously recorded and compared across the groups to account for changes attributable to the endothelium. Prior to conducting the experimental study the presence of an endothelial role was validated by testing the conducting segment of a coronary artery with acetylcholine before and after mechanical denudation of rts endothelium. Non-denuded areas were non-reactive to acetylcholine while denuded areas decreased in diameter from 14.32mm to 9.15mm, a net reduction in cross-sectional area of 59. Acetylcholine produced initial dose-dependent decreases in coronary blood flow, immediately followed by a dose-dependent hyperemia. Slopes of best-fit lines to mean values during trough and hyperemic phases were -1 .76 and 1.53, respectively. Both NTG and SP attenuated the loss of flow during cholinergic vasospasm and decreased the hyperemia that followed in the control group. Trough and hyperemia slopes were-1 .68 and 0.64 during NTG treatment and -1.45 and 1.35 during infusion of SP. In addition, trough and hyperemia flows during EDRF blockade by NOLA were respectively lower and higher than flows during the corresponding Control period. Truncated

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