NA+-K+ PUMP AND NA+-K+ COTRANSPORT IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE AND NORMOTENSIVE RATS - BASE-LINE ACTIVITY AND REGULATION

Objective: This paper examines the hypothesis that aberrations in vascular smooth muscle univalent ion transport systems play an important role in the pathogenesis of hypertension. Design: Baseline Na+-K+ pump and Na+-K+-2Cl- co-transport activities and the regulation of these ion transport systems by angiotensin 11 and second messenger molecules have been studied in cultured aortic smooth muscle cells (VSMC) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Methods. Ion transport was studied using isotopic univalent cations (Rb-86 and Na-22). Results: Baseline Na+-K+ pump activity was comparable between SHR- and WKY-derived VSMC. Baseline Na+-K+-2Cl- and K+-Cl- co-transport activity as well as K+ leakage were significantly greater in SHR VSMC. Baseline Na+-K+-2Cl- co-transport was sensitive to inhibition by forskolin and ethyleneglycol-bis-(beta-amino ethylester)-N,N,N',N'-tetraacetic acid, whereas cyclic guanosine monophosphate and phorbol 12-myristate, 13-acetate had no effect. Angiotensin II-stimulated Na+-K+-2Cl- co-transport activity did not differ between WKY and SHR VSMC. Angiotensin II increased Na+-K+-pump activity to a significantly greater extent in SHR VSMC. The stimulatory effect of angiotensin II upon Na+-K+ pump activity was reduced under Na+-free buffer conditions and in the presence of the Na+-H+ exchange inhibitor, ethylisopropyl amiloride. Na+-K+ pump activity was also stimulated by the protein kinase C activator, phorbol 12-myristate, 13-acetate, and this was completely inhibited under Na+-free buffer conditions. Conclusions: SHR VSMC exhibit anomalous Na+-K+-pump and Na+-K+-2Cl- co-transport activities. The influence of these univalent ion transport systems upon cellular Na+ and Ca2+ homeostasis invoke their participation in the pathogenesis of hypertension.