The role of phosphoinositide turnover in mediating the biphasic effect of angiotensin II on renal tubular transport.

Our previous studies have shown that angiotensin II (Ang II) has a dose-dependent biphasic effect on bicarbonate and sodium transport and 4-beta-phorbol-12-myristate-13-acetate can simulate the stimulatory effect of Ang II on Na+/H+ exchange in the proximal convoluted tubules (PCT) of the rat kidney. This study was designed to further investigate the possible role of phosphoinositide turnover in mediating the biphasic effect of Ang II. Rat PCT was perfused in vivo with Ringer's solution containing [3H]inulin as a volume marker. Bicarbonate flux (JHCO3) was determined by total CO2 changes between the collected fluid and the original perfusate as analyzed by microcalorimetry. Luminal perfusion with 10(-11) M Ang II or 10(-8) M 4-beta-phorbol-12-myristate-13-acetate stimulated both fluid reabsorption (JV) and JHCO3, these effects can be blocked by 2 x 10(-4) M 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), a blocker of intracellular calcium mobilization. Interestingly, Ang II at 10(-9) M or 2 x 10(-4) M TMB-8 have no effect on JV or JHCO3 individually. However, JV and JHCO3 significantly decreased when PCT were perfused simultaneously with 10(-9) M Ang II and 10(-4) M 1-(5-isoquinolinesulfonyl)-2-methylpiperazine; whereas JV and JHCO3 significantly increased when PCT were perfused with 10(-9) M Ang II and 2 x 10(-4) M TMB-8 together. These results suggest that PKC and intracellular calcium play a critical role in mediating the biphasic effect of Ang II on bicarbonate and sodium transport in PCT.