Mechanism of angiotensin II action on proximal tubular transport.
Our previous studies have shown that a low dose of angiotensin II (Ang II) stimulates fluid and bicarbonate absorption from the apical side of rat proximal tubule (PCT). These effects can be blocked by Ang II antagonist, (Sar1, Ile8)Ang II. The cellular mechanism underlying Ang II action, however, remained unclear. Thus, this study was designed to investigate the possible role of phosphoinositide turnover in mediating this action of angiotensin. 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 of 10(-11) M Ang II stimulated both JHCO3 and fluid reabsorption. These effects could be blocked by 10(-3) M amiloride and 10(-5) M ethylisopropylamiloride. Luminal perfusion of 4 beta-phorbol-12-myristate-13-acetate (10(-8) M) also stimulated both fluid reabsorption and JHCO3. These effects could also be blocked by amiloride and ethylisopropylamiloride. When both Ang II (10(-11) M) and 4 beta-phorbol-12-myristate-13-acetate (10(-8) M) were perfused together, the stimulatory effects on fluid reabsorption and JHCO3 were not additive. These results suggest that Ang II interacts with its receptors on the apical membrane leading to modulation of the Na-H exchange mechanism in PCT. The phosphoinositide turnover may play an important role in the Ang II action on PCT transport.
Wang
T
T
Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago.
Chan
Y L
YL
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000804:Angiotensin II; D000584:Amiloride; D012964:Sodium; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C039614:ethylisopropylamiloride