Potassium and activity of the sodium hydrogen exchanger isoform 1 in vascular smooth muscle of hypertensive rats

Low potassium intake is inversely associated with blood pressure. In vitro, the proliferation of vascular smooth muscle cells (VSMCs) shows an inverse correlation with [K+]. In hypertension, many studies have established that the ubiquitous Na+/H+ exchanger isoform 1 (NHE-1) exhibits increased activity and is permissive for cell proliferation. Changes in extracellular [K+] lead to altered intracellular Na+ content, which could affect NHE activity and NHE-1 protein expression. We therefore investigated the effects of altering extracellular [K+] on NHE activity and NHE-1 expression in cultured VSMCs of both the spontaneously hypertensive rat (SHR) and its normotensive Wistar-Kyoto counterpart (WKY). Culture of SHR VSMCs for 48 hours in media containing 2, 4, 6, and 8 mmol L-1 [K+] led to activation of NHE-1 in the low [K+] media (NHE-1 activity at [K+] 2, 4, 6, and 8 mmol L-1 were 34.3 +/- 1.7, 29.5 +/- 1.1. 27.7 +/- 1.4, and 26.1 +/- 2.1 mmol L-1 min(-1), P < .006 by analysis of variance [ANOVA]). This was not associated with any significant changes in intracellular pH. By contrast, WKY VSMCs did not exhibit any significant activation of NHE-1 in low [K+] media (NHE-1 activity at [K+] 2, 4, 6, and 8 mmol L-1 were 24.3 +/- 2.9, 22.3 +/- 1.7, 19.0 +/- 1.8 and 18.6 +/- 1.6 mmol(.)l(-1) min(-1), P = not significant [NS] by ANOVA), Culture of SHR or WKY VSMCs in low [K+] media did not alter NHE-1 protein expression, suggesting the enhancement of activity in SHR cells was due to an increased turnover number of NHE-1. This response of NHE-1 in SHR VSMCs to K+ depletion indicated a direct effect on these cells and could potentially enhance the contractile or proliferative phenotype of these cells in vivo. Copyright (C) 2001 by W.B. Saunders Company.