Human coronary arteriolar dilation to bradykinin depends on membrane hyperpolarization : Contribution of nitric oxide and Ca2+-activated K+ channels

K+ channel activation in vascular smooth muscle cells (VSMCs) plays a key role in regulating vascular tone. It has been proposed that endothelium-derived hyperpolarizing factor (EDHF) contributes to microvascular dilation more than nitric oxide (NO) does. Whether hyperpolarization is important for c...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1999-06, Vol.99 (24), p.3132-3138
Main Authors: MIURA, H, YANPING LIU, GUTTERMAN, D. D
Format: Article
Language:English
Subjects:
Adult
Aged
Apamin - pharmacology
Biological and medical sciences
Blood vessels and receptors
Bradykinin - pharmacology
Calcium - physiology
Charybdotoxin - pharmacology
Coronary Vessels - drug effects
Coronary Vessels - physiology
Cyclooxygenase Inhibitors - pharmacology
Electrophysiology
Endothelin-1 - pharmacology
Endothelium, Vascular - chemistry
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Enzyme Inhibitors - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Humans
In Vitro Techniques
Indomethacin - pharmacology
Male
Membrane Potentials - drug effects
Membrane Potentials - physiology
Middle Aged
Muscle, Smooth, Vascular - chemistry
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - physiology
NG-Nitroarginine Methyl Ester - pharmacology
Nitric Oxide - metabolism
Nitroprusside - pharmacology
Potassium Channel Blockers
Potassium Channels - physiology
Potassium Chloride - pharmacokinetics
Vasodilation - drug effects
Vasodilator Agents - pharmacology
Vertebrates: cardiovascular system
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Summary:K+ channel activation in vascular smooth muscle cells (VSMCs) plays a key role in regulating vascular tone. It has been proposed that endothelium-derived hyperpolarizing factor (EDHF) contributes to microvascular dilation more than nitric oxide (NO) does. Whether hyperpolarization is important for coronary arteriolar dilation in humans is not known. Bradykinin (BK), an endogenous vasoactive substance, is released from ischemic myocardium and regulates coronary resistance. Therefore, we tested the effects of inhibiting NO synthase, cyclooxygenase, and K+ channels on the changes in diameter and membrane potential (Em) in response to BK in isolated human coronary microvessels. Arterioles (97+/-4 micrometers; n=120) dissected from human right atrial appendages (n=78) were cannulated at a distending pressure of 60 mm Hg and zero flow. Changes in vessel diameter (video microscopy) and VSMC Em (glass microelectrodes) were measured simultaneously. In vessels constricted and depolarized (Em; -50+/-3 to -28+/-2 mV) with endothelin-1 (ET), dilation to BK was associated with greater membrane hyperpolarization (-48+/-3 mV at 10(-6) mol/L) than dilation to sodium nitroprusside (SNP) (-34+/-2 mV at 10(-4) mol/L) for similar degrees of dilation. Treatment with Nomega-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/L), an NO synthase inhibitor, partially decreased dilation to BK (maximum dilation 61+/-10% versus control 92+/-4%; P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.CIR.99.24.3132