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ANG II reduces net acid secretion in rat outer medullary collecting duct

²Division of Renal Diseases and Hypertension, University of Texas, Medical School at Houston, Houston, Texas 77030; and ¹Renal Division, Emory University School of Medicine, Atlanta, Georgia 30322

Submitted 12 November 2002 ; accepted in final form 30 June 2003

In rat outer medullary collecting duct (OMCD), the mechanism(s) and regulation of H⁺ secretion are not understood fully. The effect of changes in acid-base balance and the renin-angiotensin system on net H⁺ secretion was explored. Rats received NaCl, NaHCO₃, NH₄Cl, or nothing in their drinking water for 7 days. Total ammonia and total CO₂ (J_tCO2) fluxes were measured in OMCD tubules perfused in vitro from rats in each treatment group. J_tCO2 was reduced in tubules from rats drinking NH₄Cl relative to those drinking NaHCO₃. Because NH₄Cl intake increases plasma renin and aldosterone, we asked if upregulation of the renin-angiotensin system reduces net H⁺ secretion. Deoxycorticosterone pivalate administered in vivo did not affect J_tCO2. However, ANG II given in vivo at 0.1 ng/min reduced J_tCO2 by 35%. To determine if ANG II has a direct effect on acid secretion, J_tCO2 was measured with ANG II applied in vitro. ANG II (10^-8 M) present in the bath solution reduced J_tCO2 by 35%. This ANG II effect was not observed in the presence of the AT₁ receptor blocker candesartan. In conclusion, in rat OMCD, J_tCO2 is paradoxically reduced with NH₄Cl ingestion. Increased circulating ANG II, as occurs during metabolic acidosis, reduces J_tCO2.

ammonium; acidification; angiotensin 2; aldosterone; metabolic acidosis; metabolic alkalosis

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