Flow-induced dilation of human coronary arterioles: important role of Ca(2+)-activated K(+) channels. Circulation 2001 Apr 17;103(15):1992-8
Date
04/18/2001Pubmed ID
11306529DOI
10.1161/01.cir.103.15.1992Abstract
BACKGROUND: Flow-induced vasodilation (FID) is a physiological mechanism for regulating coronary flow and is mediated largely by nitric oxide (NO) in animals. Because hyperpolarizing mechanisms may play a greater role than NO in the microcirculation, we hypothesized that hyperpolarization contributes importantly to FID of human coronary arterioles.
METHODS AND RESULTS: Arterioles from atria or ventricles were cannulated for videomicroscopy. Membrane potential of vascular smooth muscle cells (VSMCs) was measured simultaneously. After constriction with endothelin-1, increases in flow induced an endothelium-dependent vasodilation. Nomega-Nitro-L-arginine methyl ester 10(-4) mol/L modestly impaired FID of arterioles from patients without coronary artery disease (CAD), whereas no inhibition was seen in arterioles from patients with CAD. Indomethacin 10(-5) mol/L was without effect, but 40 mmol/L KCl attenuated maximal FID. Tetraethylammonium 10(-3) mol/L but not glibenclamide 10(-6) mol/L reduced FID. Charybdotoxin 10(-8) mol/L impaired both FID (15+/-3% versus 75+/-12%, P<0.05) and hyperpolarization (-32+/-2 mV [from -28+/-2 mV after endothelin-1] versus -42+/-2 mV [-27+/-2 mV], P<0.05). Miconazole 10(-6) mol/L or 17-octadecynoic acid 10(-5) mol/L reduced FID. By multivariate analysis, age was an independent predictor for the reduced FID. Conclusions-We conclude that shear stress induces endothelium-dependent vasodilation, hyperpolarizing VSMCs through opening Ca(2+)-activated K(+) channels in human coronary arterioles. In subjects without CAD, NO contributes to FID. NO and prostaglandins play no role in patients with CAD; rather, cytochrome P450 metabolites are involved. This is consistent with a role for endothelium-derived hyperpolarizing factor in FID of the human coronary microcirculation.
Author List
Miura H, Wachtel RE, Liu Y, Loberiza FR Jr, Saito T, Miura M, Gutterman DDMESH terms used to index this publication - Major topics in bold
Age FactorsArterioles
Blood Flow Velocity
Calcium
Charybdotoxin
Coronary Vessels
Endothelin-1
Enzyme Inhibitors
Fatty Acids, Unsaturated
Female
Glyburide
Humans
In Vitro Techniques
Male
Membrane Potentials
Miconazole
Middle Aged
Multivariate Analysis
Potassium Channel Blockers
Potassium Channels
Potassium Chloride
Stress, Mechanical
Tetraethylammonium
Vasodilation