Mauban Joseph R H, Wier W Gil
Department of Physiology, University of Maryland, Baltimore, MD 21201, USA.
Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H608-16. doi: 10.1152/ajpheart.01084.2003. Epub 2004 Apr 1.
The possible roles of endothelial intracellular Ca(2+) concentration (Ca(2+)), nitric oxide (NO), arachidonic acid (AA) metabolites, and Ca(2+)-activated K(+) (K(Ca)) channels in adrenergically induced vasomotion were examined in pressurized rat mesenteric arteries. Removal of the endothelium or buffering Ca(2+) selectively in endothelial cells with BAPTA eliminated vasomotion in response to phenylephrine (PE; 10.0 microM). In arteries with intact endothelium, inhibition of NO synthase with N(omega)-nitro-l-arginine methyl ester (l-NAME; 300.0 microM) or N(omega)-nitro-l-arginine (l-NNA; 300.0 microM) did not eliminate vasomotion. Neither inhibition of cGMP formation with 10.0 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) nor inhibition of prostanoid formation (10.0 microM indomethacin) eliminated vasomotion. Similarly, inhibition of AA cytochrome P-450 metabolism with an intraluminal application of 17-octadecynoic acid (17-ODYA) or 6-(2-propargyloxyphenyl)hexanoic acid (PPOH) failed to eliminate vasomotion. In contrast, intraluminal application of the K(Ca) channel blockers apamin (250.0 nM) and charybdotoxin (100.0 nM), together, abolished vasomotion and changed synchronous Ca(2+) oscillations in smooth muscle cells to asynchronous propagating Ca(2+) waves. Apamin, charybdotoxin, or iberiotoxin (100.0 nM) alone did not eliminate vasomotion, nor did the combination of apamin and iberiotoxin. The results show that adrenergic vasomotion in rat mesenteric arteries is critically dependent on Ca(2+)-activated K(+) channels in endothelial cells. Because these channels (small- and intermediate-conductance K(Ca) channels) are a recognized component of EDHF, we conclude therefore that EDHF is essential for the development of adrenergically induced vasomotion.
在压力负荷下的大鼠肠系膜动脉中，研究了内皮细胞内钙离子浓度（Ca(2+)）、一氧化氮（NO）、花生四烯酸（AA）代谢产物以及钙激活钾离子（K(Ca)）通道在肾上腺素能诱导的血管运动中的可能作用。去除内皮或用BAPTA选择性缓冲内皮细胞内的Ca(2+)可消除对去氧肾上腺素（PE；10.0微摩尔）的血管运动反应。在具有完整内皮的动脉中，用N(ω)-硝基-L-精氨酸甲酯（L-NAME；300.0微摩尔）或N(ω)-硝基-L-精氨酸（L-NNA；300.0微摩尔）抑制一氧化氮合酶并不能消除血管运动。用10.0微摩尔1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）抑制环鸟苷酸形成或用10.0微摩尔吲哚美辛抑制前列腺素形成均不能消除血管运动。同样，通过腔内应用17-十八炔酸（17-ODYA）或6-(2-炔丙氧基苯基)己酸（PPOH）抑制AA细胞色素P-450代谢也未能消除血管运动。相反，腔内应用K(Ca)通道阻滞剂蜂毒明肽（250.0纳摩尔）和大蝎毒素（100.0纳摩尔）可共同消除血管运动，并将平滑肌细胞中的同步钙离子振荡转变为异步传播的钙离子波。单独使用蜂毒明肽、大蝎毒素或iberiotoxin（100.0纳摩尔）均不能消除血管运动，蜂毒明肽和iberiotoxin联合使用也不能消除血管运动。结果表明，大鼠肠系膜动脉中的肾上腺素能血管运动严重依赖于内皮细胞中的钙激活钾离子通道。由于这些通道（小电导和中电导K(Ca)通道）是公认的内皮衍生超极化因子（EDHF）的组成部分，因此我们得出结论，EDHF对于肾上腺素能诱导的血管运动的发展至关重要。
