Regulation of sodium-hydrogen exchange in vascular smooth muscle

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.