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

Recent micropuncture studies showed the existence of high concentratio ns of angiotensin II (ANG II) in proximal tubular fluid. In the presen t study, we have examined the effect of luminal ANG II, alone and in c ombination with peritubular ANG II, on fluid transport (J(v)) in the i solated perfused rabbit proximal convoluted tubule. In comparison with peritubular ANG II, luminal ANG II caused a similar but more potent b iphasic effect on J(v). At 10(-11) M, luminal ANG II maximally increas ed J(v) to 204 +/- 22% of the baseline compared with 142 +/- 10% by pe ritubular 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 peritu bular ANG II. When luminal and peritubular ANG II were combined at con centrations that impose similar effect on J(v), the effects of luminal and peritubular ANG II were not additive. However, when combined at c oncentrations that would otherwise impose opposing effects on J(v), th e stimulatory effect predominated. In support of the role of apical ph ospholipase A(2) (PLA(2)) on the effect of luminal ANG II, ANG II stim ulated 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 tubu le J(v) involving activation of brush-border membrane PLA(2). When com bined, luminal and peritubular ANG II exert their effects in concert o n proximal tubule J(v).