Endothelial Mediation of Coronary Vascular Tone: Nitric Oxide Attenuation of Cholinergic Vasospastic Challenge
Abstract
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 only)and after infusion of substance P (SP+ACh), an endothelial-dependent vasodilator, and nitroglycerin (NTG+ACh), 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 oxide(NO) produced by vascular endothelium. The hemodynamic parameters of mean and phasic coronary artery flows, arterial and intraventricular pressures, dP/dt 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]
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1993
- Accession Number
- AD1011160
Entities
People
- Neil W. Ahle
Organizations
- Uniformed Services University of the Health Sciences