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WATER AND ELECTROLYTE HOMEOSTASIS

Effect of chronic inhibition of converting enzyme on proximal tubule acidification

Centro de Estudios en Salud y Medio Ambiente, Escuela de Ciencia y Tecnología, Universidad Nacional de Gral, San Martín, Argentina

Submitted 15 August 2007 ; accepted in final form 8 April 2008

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_HCO3^–). 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_HCO3^–. Nitric oxide (NO^·) synthesis in kidney cortex homogenates was assessed by quantifying the conversion of [¹⁴C]-L-arginine to [¹⁴C]-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 a 50% increase in J_HCO3^–. Luminal perfusion with ethyl-isopropyl amiloride (EIPA) 10^–4M or bafilomycin 10^–6M decreased J_HCO3^– by 60% and 30%, respectively, in both control and enalapril-treated rats. The effect of EIPA and bafilomycin on absolute J_HCO3^– was larger in enalapril-treated than in control rats. Acute inhibition of NO^· synthesis with N^G-nitro-L-arginine methyl esther abolished the enalapril-induced increase in J_HCO3^–. 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.

enalapril; Na⁺/H⁺ exchange; V-H⁺ATPase; micropuncture experiments; NO^· synthase activity