Angiographic assessment of human coronary artery endothelial function by measurement of endothelium-dependent vasodilation

Abstract

In isolated atherosclerotic human coronary arteries endothelium-dependent vascular relaxation is abolished with acetylcholine whereas another EDRF-dependent vasodilator, substance P, still produces significant relaxation. To study further these in vitro findings, graded doses of acetylcholine and substance P, which produced no systemic effects, were infused into the left anterior descending artery of patients with angiographically moderate coronary artery disease. The effects of acetylcholine and substance P on LAD diameter were analysed by quantitative angiography. Generally, acetylcholine caused no relaxation but concentration-dependent contraction from 1.67 +/- 0.06 mm to 1.45 +/- 0.09 mm (P less than 0.01), whereas substance P dilated the arteries to 1.89 +/- 0.10 mm (P less than 0.01). In contrast, both drugs caused a marked increase in great cardiac vein oxygen saturation, indicating an increase of coronary flow. The results suggest that the failure of the atherosclerotic epicardial human coronary artery to vasodilate in response to acetylcholine represents a muscarinic endothelial defect. The preserved vasodilation with substance P in the presence of a refractoriness to acetylcholine suggests that atherosclerotic human coronary endothelial cells exposed to appropriate non-muscarinic stimuli are still capable to release EDRF and that atherosclerotic smooth muscle retains a responsive receptor mechanism for EDRF.

Growth-promoting effects of substance P on endothelial cells in vitro. Synergism with calcitonin gene-related peptide, insulin, and plasma factors.

“…These effects include its role in stimulating immune function,14 tissue repair,15 increased vascular permeability,16"17 response to hypoxia3 and its role as a mediator of inflammation,18 potent peripheral and coronary vasodilator, and modulator of coronary blood flow.19-22 The two latter effects are associated with SP-mediated endothelial prostacyclin (PGI2) production23'24 and endothelium-dependent production of endothelium-derived relaxing factor (EDRF). 25,26 Evidence from recent studies27-29 suggests that sensory neuropeptides may also play an important role in regulating in vitro cellular proliferation. However, the role of SP on arterial endothelial cell growth is unknown.…”

“…[19][20][21][22] The two latter effects are associated with SP-mediated endothelial prostacyclin (PGI2) production23'24 and endothelium-dependent production of endothelium-derived relaxing factor (EDRF). 25,26 Evidence from recent studies27-29 suggests that sensory neuropeptides may also play an important role in regulating in vitro cellular proliferation. However, the role of SP on arterial endothelial cell growth is unknown.…”

Elimination of variable vasomotor tone in studies with repeated quantitative coronary angiography

“…Vasoactive drugs should be withdrawn in due time prior to all quantitative coronary angiographic studies. Other factors influencing CVT, such as catecholamines, metabolites, changes of blood pH, changes of coronary flow or endogenous substances modifying the release of EDRF in the coronary arterial endothelium should be considered and be kept as constant as possible [15,16,18,[31][32][33][34][35][36].…”

Comparison of Nitric Oxide Production in Response to Carbachol Between Macrovascular and Microvascular Cardiac Endothelial Cells.

“…It has been demonstrated that endotheliumdependent vasodilation is impaired in several pathological conditions including atherosclerosis and hypertension. [23][24][25] The endothelium has a significantly heterogeneous structure and function among organs, and there are differences between macrovascular and microvascular endothelium. 26 A number of studies have shown that cardiac microvascular EC play important roles in physiological and pathological conditions such as hypertrophy, ischemia and collateral development.…”