Effect of chronic inhibition of converting enzyme on proximal tubule acidification.
The acute effect of angiotensin-converting enzyme inhibition (ACEi) on proximal convoluted tubule (PCT) function is well documented. However, the effect of chronic treatment is less known. The aim of this work was to evaluate the effect of chronic ACEi on PCT acidification (J(HCO(3)(-))). Rats received enalapril (10 mg.kg(-1).day(-1), added to the drinking water) during 3 mo. Micropuncture experiments were performed to measure the effect of chronic ACEi on J(HCO(3)(-)). Nitric oxide (NO.) synthesis in kidney cortex homogenates was assessed by quantifying the conversion of [(14)C]-L-arginine to [(14)C]-L-citrulline. Western blot analysis was performed to determine the abundances of V-H(+)ATPase and NHE3 isoform of the Na(+)/H(+) exchanger in proximal brush-border membrane vesicles (BBMV). Enalapril treatment induced an approximately 50% increase in J(HCO(3)(-)). Luminal perfusion with ethyl-isopropyl amiloride (EIPA) 10(-4)M or bafilomycin 10(-6)M decreased J(HCO(3)(-)) by approximately 60% and approximately 30%, respectively, in both control and enalapril-treated rats. The effect of EIPA and bafilomycin on absolute J(HCO(3)(-)) was larger in enalapril-treated than in control rats. Acute inhibition of NO. synthesis with N(G)-nitro-L-arginine methyl ester abolished the enalapril-induced increase in J(HCO(3)(-)). Cortex homogenates from enalapril-treated rats displayed a 46% increase in nitric oxide synthase (NOS) activity compared with those from untreated animals. Enalapril treatment did not affect the abundances of NHE3 and V-H(+)ATPase in BBMV. Our results suggest that PCT acidification is increased during chronic ACEi probably due to an increase in NO. synthesis, which would stimulate Na(+)/H(+) exchange and electrogenic proton transport.
Diaz-Sylvester
Paula L
PL
CESyMA, ECyT, Universidad Nacional de Gral. San Martín, Avenida Gral Paz 5445, 1650 San Martín, Buenos Aires, Argentina.
Fiori
Mariana C
MC
Dieguez
Stella M
SM
Müller
Angélica C
AC
Lopardo
Mariano L
ML
Amorena
Carlos E
CE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D004656:Enalapril / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D002956:Citrulline; D009569:Nitric Oxide; D004656:Enalapril; D001120:Arginine; D007703:Peptidyl-Dipeptidase A; D025262:Vacuolar Proton-Translocating ATPases