ANGIOTENSIN-II MODULATES CELLULAR FUNCTIONS OF PODOCYTES

The aim of this study was to examine the effects of angiotensin II (An g II) on membrane voltage (V-m) and cytosolic calcium activity ([Ca2+] (i)) of rat podocytes. To approach better the in vivo situation, we ha ve developed an experimental approach that allows podocytes to be stud ied in the intact microdissected glomerulus. Ang IT depolarized podocy tes in the glomerulus (EC50 15 nM N = 49). Lilts podocytes in the glom erulus, podocytes in short-term culture also depolarized in response t o Ang II (10 nM, N = 5). Ang II increased [Ca2+](i) in podocytes in cu lture (EC50 3 nM, N = 229). In a solution with reduced extracellular [ Ca2+] (10 mu M), Ang II-mediated [Ca2+](i) increase was significantly reduced by 60% +/- 20% (N = 12). Flufenamate, an inhibitor of nonselec tive ion channels, inhibited Ang II-mediated increase of [Ca2+](i) (IC 50 20 mu M, N = 29). The Ang subtype 1 (AT1) receptor antagonist losar tan inhibited both Ang II-mediated depolarization and [Ca2+](i) increa se in podocytes (N = 5 to 35). Our results support the concept that An g II might influence podocyte function directly via an AT1 receptor.