Lucchesi P A, Berk B C
Division of Cardiology, Emory University, Atlanta, Georgia, USA.
Cardiovasc Res. 1995 Feb;29(2):172-7.
The Na+/H+ exchanger in vascular smooth muscle cells represents a major mechanism for sodium influx and is also one of the principal mechanisms responsible for the regulation of intracellular pH (pHi). In this review, the relationship between pHi and vascular smooth muscle cell growth, the regulation of Na+/H+ exchange by vasoactive agents and growth factors, and the second messenger pathways that may be involved in activation of Na+/H+ exchange have been discussed. The exchanger appears to be important in vascular smooth muscle cell growth, based on results that (1) Na+/H+ exchange is stimulated by hypertrophic and hyperplastic agonists, (2) vascular smooth muscle cell proliferation is induced by cytoplasmic alkalinisation in the absence of mitogens, (3) vascular smooth muscle cell proliferation is dependent on extracellular sodium, and (4) inhibitors of Na+/H+ exchange block cell growth. Several pathways appear capable of activating the exchanger in vascular smooth muscle cells as there is evidence for both calcium and protein kinase C dependent and independent pathways. We speculate that the calcium and protein kinase C dependent pathways may play a role in the contractile response of differentiated vascular smooth muscle cells in the vessel wall, while the calcium and protein kinase C independent pathways may be involved in the proliferative response observed after arterial injury and in tissue culture.
血管平滑肌细胞中的钠氢交换体是钠内流的主要机制，也是调节细胞内pH值（pHi）的主要机制之一。在这篇综述中，讨论了pHi与血管平滑肌细胞生长之间的关系、血管活性药物和生长因子对钠氢交换的调节，以及可能参与钠氢交换激活的第二信使途径。基于以下结果，该交换体在血管平滑肌细胞生长中似乎很重要：（1）肥大和增生性激动剂可刺激钠氢交换；（2）在没有有丝分裂原的情况下，细胞质碱化可诱导血管平滑肌细胞增殖；（3）血管平滑肌细胞增殖依赖于细胞外钠；（4）钠氢交换抑制剂可阻断细胞生长。由于有证据表明存在钙和蛋白激酶C依赖性及非依赖性途径，因此有几种途径似乎能够激活血管平滑肌细胞中的交换体。我们推测，钙和蛋白激酶C依赖性途径可能在血管壁中分化的血管平滑肌细胞的收缩反应中起作用，而钙和蛋白激酶C非依赖性途径可能参与动脉损伤后和组织培养中观察到的增殖反应。
