ANGIOTENSIN-II INDUCES CHANGES IN THE CYTOSOLIC SODIUM CONCENTRATION IN BOVINE ADRENAL GLOMERULOSA CELLS - INVOLVEMENT IN THE ACTIVATION OFALDOSTERONE BIOSYNTHESIS

The homeostasis of cytosolic free calcium ([Ca2+]i) and intracellular free sodium ([Na+]i) are linked in many cell types. We, therefore, stu died the effect on [Na+]i of two physiological stimulators of aldoster one synthesis that trigger the calcium messenger system, angiotensin-I I (Ang II) and potassium ion (K+), in cultured bovine adrenal glomerul osa cells, using the intracellular fluorescent probe for sodium, sodiu m benzofuran isophthalate. Ang II induced a concentration-dependent an d sustained increase in [Na+]i, from a resting value of 9.2 +/- 3.5 to a maximum of 48.5 +/- 5.5 mm (n = 14). This [Na+]i response was media ted by receptors of the AT1 subtype, because it was abolished by losar tan (DuP 753). K+ (15 mm) induced a weaker [Na+]i response, from 5.9 /- 2.6 to 16.8 +/- 2.5 mm (n = 9). In freshly prepared cells, basal [N a+]i was significantly higher (23.9 +/- 1.8 mm; n = 14; P < 0.01) than in cultured cells. Atrial natriuretic peptide, which is known to affe ct sodium transport in various cell types, did not alter the [Na+]i re sponse elicited by Ang II. Ethylisopropylamiloride, an inhibitor of Na +/H+ exchange, and dichlorobenzamyl, an inhibitor of Na+/Ca2+ exchange , both inhibited in a concentration-dependent manner the Ang II- and K +-induced aldosterone response. Isoosmotic replacement of extracellula r Na+ markedly reduced basal aldosterone synthesis. Under these condit ions, the concentration-response curve for Ang II-induced aldosterone synthesis was shifted to the right, and its maximum was strikingly dim inished. These results show that Ang II and, to a lesser extent, K+ in duce significant changes in [Na+]i in bovine glomerulosa cells. These [Na+]i changes probably occur through the Na+/H+ and Na+/Ca2+ exchange rs and are likely to play a role in activation of the steroidogenic ca scade.