Na-H exchange is a major pathway for Na influx in rat vascular smooth muscle

Abstract

Rat aortic segments and aortic smooth muscle cells in primary culture were used to examine the importance of the Na-H exchange system in transporting Na into smooth muscle. Ethylisopropylamiloride was approximately 100 times more potent than amiloride at inhibiting Na influx into smooth muscle. In a 135 mM Na-containing medium approximately 80% of the Na influx rate could be inhibited by 100 microM ethylisopropylamiloride. The rate of Na entry into cells was markedly influenced by extracellular and intracellular pH. Elevating extracellular pH from 6.0 to 8.0 increased the Na influx rate. The dependence of the Na influx rate on intracellular pH was demonstrated by acidification of cells with nigericin or preincubation with ammonium chloride. These two procedures increased 22Na+ influx rate by about 3.5-fold. In both instances the increases in 22Na+ influx rate could be completely attenuated by ethylisopropylamiloride. Increases in Na influx rate via the Na-H exchange also increased the activity of the Na-K pump, thereby maintaining intracellular Na content approximately constant. These results indicate that Na-H exchange is a major influx pathway for Na in rat vascular smooth muscle. Activation of this system activates the Na-K pump, which maintains intracellular Na constant.

Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C.

“…The glucose-induced increase in Na' uptake by VSMC was sustained with continued exposure to the high-glucose medium for up to 24 h. Na+/ H' antiport activity is a major pathway for Na' influx in VSMC and this transport system can be inhibited by the addi- sensitive Na' uptake by VSMC. VSMC were exposed to control medium (glucose 5 mM) or high-glucose medium (glucose 20 mM) for tion of amiloride (31). Amiloride ( 1 mM) significantly reduced Na+ uptake by VSMC in the presence of control medium and completely prevented the increase in Na+ uptake previously observed in the presence ofthe elevated glucose medium at both 3 and 24 h (Fig.…”

“…The Na4/H4 antiport is a major pathway forthe regulation of Na4 uptake by VSMC (31 ). Previous studies have emphasized that the activity of Na4/H+ antiport in many cell types, including VSMC, is influenced by the activation of PKC (11,18,(36)(37)(38)(39)(40)(41)(42).…”

Transforming growth factor-beta 1 gene activation and growth of smooth muscle from hypertensive rats.

“…The identity of smooth muscle cells in our cultures was verified by immunocytochemical analysis using antibodies for smooth muscle myosin. 20 These "primary" smooth muscle cells were subsequently passaged every week and grown in 10% FCS/DMEM using 90-mm tissue culture dishes. Cells between primary and fourth passages were used in all experiments.…”

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

“…The Na+/H + exchange is not only a major way for protons to exit from vascular smooth muscle cells but also a major way for sodium entry into these cells (Little et al 1986;Rothstein 1989). Inhibition of Na+/H + exchange could therefore lead to a sink of [Na+]i, which consequently could lead to changes of the cell volume (Rothstein 1989) and probably to more important changes in the activity of systems dependent on the transmembrane sodium gradient.…”

“…Although, its functional relevance is less clear for small arteries (Mulvany and Aalkjaer 1990), the Na+/H § exchange is a major acid extruder from VSM cells and plays therefore an important role for the cytosolic pH homeostasis (Boyarsky et al 1988;Kahn et al 1990;Weissberg et al 1987). The Na+/H + exchange is also a major route for sodium entry into VSM cells and thus a major determinant for [Na+]i (Little et al 1986). Moreover, the Na+/H § exchanger has been found to be hormonally regulated in VSM cells, thus providing the possibility that this exchange system could serve as signal transduction system for the hormone control of renin secretion.…”