Inhibitory effect of angiotensin II on renal tubular transport.
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.
Chatsudthipong
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Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60680.
Chan
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YL
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D010740:Phospholipases; D002118:Calcium