Endothelial K(ca) channels mediate flow-dependent dilation of arterioles of skeletal muscle and mesentery.
The role of Ca(2+)-activated potassium channels (K(Ca)) in flow-initiated intracellular events in microvessels is not known. We hypothesized that K(Ca) channels in the arteriolar endothelium are responsible for the mechanotransduction of flow/shear stress-induced arteriolar dilation in skeletal muscle and mesentery of rats. The active diameter of arterioles isolated from gracilis (80 mm Hg) and cremaster (60 mm Hg) muscles and mesentery (80 mm Hg) at a constant intraluminal pressure was 53 +/- 3, 77 +/- 5, and 72 +/- 6 microm, respectively. Their passive diameter (in Ca(2+)-free solution) was 113 +/- 3, 152 +/- 12, and 121 +/- 7 microm, respectively. At a constant intraluminal pressure stepwise increases in perfusate flow (25, 40, and 14 microL/min in 5, 10, and 2 microL/min steps) elicited a gradual increase in diameter of all three groups of arterioles up to 93 +/- 5, 137 +/- 11, and 102 +/- 7 microm, respectively. Flow-induced dilations of arterioles were eliminated by intraluminal administration of iberiotoxin (ibTX 10(-9) M), an inhibitor of high conductance K(Ca) channels (BK(Ca)). In contrast, arteriolar dilations to acetylcholine and sodium nitroprusside were not altered by this agent, indicating that BK(Ca) channels are not involved in the receptor-mediated endothelial synthesis of nitric oxide (NO) and that the inhibitor did not affect the action of NO on smooth muscle. Abluminal application of ibTX (10(-8) M) did not affect flow-dependent dilation. We conclude that in arterioles of several tissues activation of endothelial BK(Ca) channels is an obligatory step in the transduction of the signal initiated by changes in intraluminal flow/shear stress, leading to the release of endothelial factors evoking dilation.
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
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Sun
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Huang
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Koller
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Kaley
D000818:Animals; D001160:Arterioles / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000098:blood supply; D010477:Perfusion; D015221:Potassium Channels / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000502:physiology; D013314:Stress, Mechanical; D014664:Vasodilation / Q000502:physiology*
D015221:Potassium Channels; D002118:Calcium