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Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom
Smooth
muscle membrane potential and tension in rat isolated small mesenteric
arteries (inner diameter 100-200 µm) were measured simultaneously to investigate whether the intensity of smooth muscle
stimulation and the endothelium influence responses to exogenous
K+. Variable smooth muscle depolarization and contraction
were stimulated by titration with 0.1-10 µM phenylephrine.
Raising external K+ to 10.8 mM evoked correlated, sustained
hyperpolarization and relaxation, both of which were inhibited as the
smooth muscle depolarized and contracted to around
38 mV and 10 mN,
respectively. At these higher levels of stimulation, raising the
K+ concentration to 13.8 mM still hyperpolarized and
relaxed the smooth muscle. Relaxation to endothelium-derived
hyperpolarizing factor, released by ACh, was not altered by the level
of stimulation. In endothelium-denuded arteries, the
concentration-relaxation curve to K+ was shifted to the
right but was not depressed. In denuded arteries, relaxation to
K+ was unaffected by the extent of prior stimulation and
was blocked with 0.1 mM ouabain but not with 30 µM Ba2+.
The ability of K+ to stimulate simultaneous
hyperpolarization and relaxation in the mesenteric artery is consistent
with a role as an endothelium-derived hyperpolarizing factor activating
inwardly rectifying K+ channels on the endothelium and
Na+-K+-ATPase on the smooth muscle cells.
endothelium-derived hyperpolarizing factor; membrane potential; acetylcholine; vascular smooth muscle
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