Analysis of angiotensin‐stimulated sodium transport in cultured smooth muscle cells from rat aorta

Abstract

Angiotensin peptides (AI, AII, AIII) increased the rate of Na+ accumulation by smooth muscle cells (SMC) cultured from rat aorta. The stimulatory effect of AII on Na+ uptake was observed when Na+ exodus via the Na+/K+ pump was blocked either by ouabain or by the removal of extracellular K+. AII was at least ten times more potent than AIII and about 100 times more potent than AI in stimulating Na+ uptake. Saralasin had little effect on Na+ uptake by itself but almost completely blocked the increase caused by AII. The stimulation of net Na+ entry by AI, but not AII, was prevented by protease inhibitors. The stimulation of Na+ uptake was almost completely blocked by amiloride. Tetrodotoxin, which prevented veratridine from increasing Na+ uptake, had no effect on the response to AII. Angiotensin increased the rate of ouabain-sensitive 86Rb+ uptake (Na+/K+ pump activity) but had no effect on ouabain-sensitive ATPase activity in frozen-thawed SMC or in microsomal membranes isolated from cultured SMC. The stimulation of ouabain-sensitive 86Rb+ uptake by AII was blocked by saralasin. Omitting Na+ from the external medium prevented AII from increasing 86Rb+ uptake. AII had no effect on cell volume or cyclic AMP levels in the cultured SMC. These results suggest that angiotensin peptides activate an amiloride-sensitive Na+ transporter which supplies the Na+/K+ pump with more Na+, its rate-limiting substrate.

Alterations in [Ca2+]i mediated by sodium‐calcium exchange in smooth muscle cells isolated from the guinea‐pig ureter.

“…lOB suggest it would not. In addition, [Na+]i may also increase as a result of activation by agonists in some smooth muscles (Smith & Brock, 1983;Aaronson & Jones, 1988). The driving force for reduction of [Ca2+]i via the exchange may therefore be reduced following pharmacomechanical coupling, at least until the Na+ gradient is restored.…”

Effect of catecholamines on Na/H exchange in vascular smooth muscle cells.

“…Previous studies have shown that DNA synthesis in VSMC can be stimulated by peptide growth factors (14,19,20), phorbol esters (13), and catecholamines (2). In addition, both growth factors (14, 19) and phorbol esters (13) have been shown to also stimulate Na/H exchange.…”

“…Another agent shown to be mitogenic for VSMC is angiotensin II (6). In addition, Smith et al have demonstrated that angiotensin II could activate Na/H exchange in VSMC (20). Recently, my laboratory has shown that DNA synthesis and Na/H exchange in VSMC could be stimulated by biologically active phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) (13).…”

Properties and physiologic roles of the plasma membrane sodium-hydrogen exchanger.

“…It was subsequently demonstrated that the Na+ influx is via an electroneutral and amiloride-sensitive Na+-H+ exchanger (43,(45)(46)(47) (51). The use of amiloride inhibition of cell growth to prove the importance of Na'-H' exchange has been criticized because of the ability of the drug to directly inhibit protein synthesis (52 (61), lys-bradykinin in human fibroblasts (62), and vasopressin (63). Insulin has been observed to increase Na+-H+ countertransport in skeletal muscles cells (42); in fibroblasts it has synergistic actions with EGF suggesting a different mechanism of action (59).…”