Increases in cellular sodium concentration by arginine vasopressin and endothelin in cultured rat glomerular mesangial cells.

The present study was undertaken to determine whether arginine vasopressin (AVP), angiotensin-II, and endothelin (ET) increase the cellular sodium concentration ([Na+]i) in cultured rat glomerular mesangial cells. [Na+]i was measured using the fluorescence indicator dye sodium-binding benzofuran isophthalate. These three vasoconstrictor hormones increased cellular free calcium ([Ca2+]i) and [Na+]i in a dose-dependent manner ([Na+]i: basal, 11.5; 10(-7) M AVP, 20.5; 10(-7) M angiotensin-II, 13.8; and 10(-7) M ET, 21.2 mM). The mobilization of [Ca2+]i was faster than that of [Na+]i. The AVP-induced increase in [Na+]i was completely blunted by the potent V1 antagonist d(CH2)5Tyr(Me)AVP. Vasoconstrictor hormones produced a biphasic cellular pH (pHi) change, characterized by a transient acidification, followed by a sustained alkalinization. The Ca(2+)-free condition markedly reduced AVP- and ET-induced increases in [Ca2+]i and [Na+]i and biphasic changes in pHi. In the Na(+)-free state, the hormonally mobilized [Ca2+]i was significantly enhanced. Basal [Na+]i decreased to below 3 mM, and there was little increase in [Na+]i after the addition of vasoconstrictor hormones, suggesting that the source of [Na+]i is extracellular space. Only early acidification was obtained in the absence of a sustained alkalinization. The [Na+]i mobilization was closely related to the biphasic change in pHi. These results indicate that AVP, ET, and angiotensin-II increase [Na+]i in glomerular mesangial cells, and that the early mobilization of [Na+]i depends on Na+/Ca2+ exchange, and the sustained phase depends on Na+/H+ exchange. The hormonally mobilized [Ca2+]i is essential for the activation of Na+/H+ exchange, and an increase in [Na+]i is suggested to play an important role in cellular alkalinization.