Department of Biomedicine and the Water and Salt Research Center, Aarhus University, Aarhus C, Denmark.
J Physiol. 2012 Apr 15;590(8):1895-906. doi: 10.1113/jphysiol.2011.227132. Epub 2012 Feb 20.
Acid–base transport in the vascular wall remains incompletely understood. Here, we investigated (a) implications of Na(+)/H(+) exchanger NHE1 knockout for vascular smooth muscle (VSMC) and endothelial cell (EC) pH(i) regulation, mesenteric artery morphology, vasomotor function and blood pressure regulation, and (b) consequences of sustained EC and VSMC acidification for vasomotor function. Na(+)/H(+) exchange activity was abolished in VSMCs and ECs from NHE1 knockout mice, but with CO(2)/HCO(3)(−) present, steady-state pH(i) was unaffected. Active tension was 30% smaller in arteries from NHE1 knockout than wild-type mice, and media thickness equally reduced. Number of VSMCs per unit artery length was unchanged whereas volume and cross-sectional area of individual VSMCs were reduced. Media stress, force production per VSMC cross-sectional area and VSMC Ca(2+) responses were unaffected. Blood pressure was 25 mmHg lower in NHE1 knockout than wild-type mice. Omission of CO(2)/HCO(3)(−) caused VSMCs and ECs to acidify substantially more in NHE1 knockout (0.3–0.6 pH-units) than wild-type (0.02–0.1 pH units) mice. Removing CO(2)/HCO(3)(−) inhibited acetylcholine-induced NO-mediated relaxations in arteries from NHE1 knockout but not wild-type mice. Without CO(2)/HCO(3)(−), effects of NO synthase and rho kinase inhibition on noradrenaline-induced contractions were smaller in arteries from NHE1 knockout than wild-type mice whereas the EC Ca(2+) response to acetylcholine, VSMC Ca(2+) response to noradrenaline and vasorelaxation to S-nitroso-N-acetylpenicillamine were unaffected. In conclusion, NHE1 mediates the Na(+)/H(+) exchange in ECs and VSMCs. Under physiological conditions, CO(2)/HCO(3)(−)-dependent mechanisms mask the pH(i)-regulatory function of NHE1. NHE1 knockout causes hypotrophy of VSMCs, reduced artery tension and lower blood pressure. At acidic pH(i), NO-mediated vasorelaxation and rho kinase-dependent VSMC Ca(2+) sensitivity are reduced.
酸-碱平衡转运在血管壁中的机制仍不完全清楚。在这里，我们研究了（a）血管平滑肌（VSMC）和内皮细胞（EC）pH 值调节、肠系膜动脉形态、血管舒缩功能和血压调节中钠氢交换蛋白 1（NHE1）敲除的意义，以及（b）EC 和 VSMC 持续酸化对血管舒缩功能的影响。NHE1 敲除小鼠的 VSMC 和 EC 中的钠氢交换活性被消除，但在有 CO2/HCO3-存在的情况下，稳态 pH 值不受影响。与野生型小鼠相比，NHE1 敲除小鼠的动脉主动张力降低了 30%，而血管中层厚度相等减少。单位动脉长度的 VSMC 数量不变，而单个 VSMC 的体积和横截面积减小。中层应力、每个 VSMC 横截面积的力产生和 VSMC Ca2+反应不受影响。NHE1 敲除小鼠的血压比野生型小鼠低 25mmHg。去除 CO2/HCO3-会导致 NHE1 敲除小鼠的 VSMC 和 EC 酸化程度比野生型小鼠（0.02-0.1 pH 单位）显著更高（0.3-0.6 pH 单位）。去除 CO2/HCO3-会抑制 NHE1 敲除而不是野生型小鼠的动脉中乙酰胆碱诱导的 NO 介导的松弛。没有 CO2/HCO3-，NO 合酶和 rho 激酶抑制剂对去甲肾上腺素诱导的收缩的影响在 NHE1 敲除小鼠的动脉中比野生型小鼠小，而 EC 对乙酰胆碱的 Ca2+反应、VSMC 对去甲肾上腺素的 Ca2+反应和 S-亚硝基-N-乙酰青霉胺的血管舒张不受影响。总之，NHE1 介导 EC 和 VSMC 中的钠氢交换。在生理条件下，CO2/HCO3-依赖性机制掩盖了 NHE1 的 pH 值调节功能。NHE1 敲除导致 VSMC 萎缩、动脉张力降低和血压降低。在酸性 pH 值时，NO 介导的血管舒张和 rho 激酶依赖性 VSMC Ca2+敏感性降低。
