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.
Quinn
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Department of Medicine and Therapeutics, University of Leicester, Leicester, UK.
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D000818:Animals; D001013:Aorta, Thoracic; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D020033:Protein Isoforms; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D011188:Potassium