Sun D, Huang A, Koller A, Kaley G
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
Microvasc Res. 2001 Mar;61(2):179-86. doi: 10.1006/mvre.2000.2291.
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.
钙离子激活钾通道（K(Ca)）在微血管血流引发的细胞内事件中的作用尚不清楚。我们推测，小动脉内皮中的K(Ca)通道负责在大鼠骨骼肌和肠系膜中血流/剪切应力诱导的小动脉扩张的机械转导。在恒定管腔内压力下，从股薄肌（80毫米汞柱）、提睾肌（60毫米汞柱）和肠系膜（80毫米汞柱）分离的小动脉的活性直径分别为53±3、77±5和72±6微米。它们的被动直径（在无钙溶液中）分别为113±3、152±12和121±7微米。在恒定管腔内压力下，灌注液流量逐步增加（以5、10和2微升/分钟的步长分别为25、40和14微升/分钟），导致所有三组小动脉的直径逐渐增加，分别达到93±5、137±11和102±7微米。腔内给予iberiotoxin（ibTX 10(-9) M），一种高电导K(Ca)通道（BK(Ca)）的抑制剂，可消除血流诱导的小动脉扩张。相反，该药物不会改变小动脉对乙酰胆碱和硝普钠的扩张，表明BK(Ca)通道不参与受体介导的内皮一氧化氮（NO）合成，且该抑制剂不影响NO对平滑肌的作用。腔外应用ibTX（10(-8) M）不影响血流依赖性扩张。我们得出结论，在几种组织的小动脉中，内皮BK(Ca)通道的激活是腔内血流/剪切应力变化引发信号转导的必要步骤，导致内皮因子释放引起扩张。
