AJP - Renal Physiology, Vol 260, Issue 3 340-F346, Copyright © 1991 by American Physiological Society
Inhibitory effect of angiotensin II on renal tubular transport
V. Chatsudthipong and Y. L. Chan
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60680.
This study was designed to examine the intracellular mechanism of
inhibitory action of high concentration of angiotensin II (ANG II) on
proximal tubular transport in rat kidneys by microperfusion methods.
Perfusion of ANG II (10(-6) M) to peritubular capillaries caused a
reduction of both fluid and HCO3- transport (Jv and JHCO3-, respectively)
by 33 and 26%, respectively. These inhibitory effects were blocked by the
ANG II-receptor antagonist [Sar1, Ile8]ANG II (10(-5) M). Similar degrees
of inhibition on Jv and JHCO3- were observed when ionomycin (10(-7) and
10(-6) M), a Ca2+ ionophore, was added to capillary perfusate. Moreover,
there was no additive effect when both ANG II and ionomycin were perfused
together through capillaries, suggesting that both agents work via the same
mechanism, presumably by increasing cytosolic Ca2+ concentration ([Ca2+]i).
Inhibitory effects of ANG II on proximal tubular transport were still
observed in a Ca2(+)-free perfusate containing ethylene
glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, indicating
that these effects do not require influx of Ca2+ from extracellular medium.
Furthermore, the observation that TMB-8, an agent that prevents
intracellular Ca2+ mobilization, completely eliminated the effect of ANG II
strongly suggests that intracellular Ca2+ rather than Ca2+ influx mediates
effects of ANG II on proximal tubular transport. Direct measurement of
[Ca2+]i by use of fura-2 in isolated proximal tubular cells showed slight
but statistically significant increases in [Ca2+]i. Taken together, these
observations support the idea that intracellular Ca2+ serves as a second
messenger in the inhibitory effect of high concentrations of ANG II on Jv
and JHCO3- in proximal tubule of kidney.
