EFFECT OF LUMINAL ANGIOTENSIN-II ON PROXIMAL TUBULE FLUID TRANSPORT - ROLE OF APICAL PHOSPHOLIPASE A(2)

Recent micropuncture studies showed the existence of high concentrations of angiotensin II (ANG II) in proximal tubular fluid. In the present study, we have examined the effect of luminal ANG II, alone and in combination with peritubular ANG II, on fluid transport (J(v)) in the isolated perfused rabbit proximal convoluted tubule. In comparison with peritubular ANG II, luminal ANG II caused a similar but more potent biphasic effect on J(v). At 10(-11) M, luminal ANG II maximally increased J(v) to 204 +/- 22% of the baseline compared with 142 +/- 10% by peritubular ANG II at 10(-10) M. At 10(-8) M, luminal ANG II suppressed J(v) to 9.7 +/- 16% of the baseline compared with 64 +/- 14% by peritubular ANG II. When luminal and peritubular ANG II were combined at concentrations that impose similar effect on J(v), the effects of luminal and peritubular ANG II were not additive. However, when combined at concentrations that would otherwise impose opposing effects on J(v), the stimulatory effect predominated. In support of the role of apical phospholipase A(2) (PLA(2)) on the effect of luminal ANG II, ANG II stimulated PLA(2) activity in isolated brush-border membrane vesicles, and addition of PLA(2) inhibitor, mepacrine or dibucaine, to the luminal perfusate attenuated the effect of luminal ANG II on J(v). In summary, these studies show a potent effect of luminal ANG II on proximal tubule J(v) involving activation of brush-border membrane PLA(2). When combined, luminal and peritubular ANG II exert their effects in concert on proximal tubule J(v).