Nitric oxide reduces Clâ» absorption in the mouse cortical collecting duct through an ENaC-dependent mechanism.
Am J Physiol Renal Physiol
; 304(11): F1390-7, 2013 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-23515718
ABSTRACT
Since nitric oxide (NO) participates in the renal regulation of blood pressure, in part, by modulating transport of Na⺠and Clâ» in the kidney, we asked whether NO regulates net Clâ» flux (JCl) in the cortical collecting duct (CCD) and determined the transporter(s) that mediate NO-sensitive Clâ» absorption. Clâ» absorption was measured in CCDs perfused in vitro that were taken from aldosterone-treated mice. Administration of an NO donor (10 µM MAHMA NONOate) reduced JCl and transepithelial voltage (VT) both in the presence or absence of angiotensin II. However, reducing endogenous NO production by inhibiting NO synthase (100 µM N(G)-nitro-L-arginine methyl ester) increased JCl only in the presence of angiotensin II, suggesting that angiotensin II stimulates NO synthase activity. To determine the transport process that mediates NO-sensitive changes in JCl, we examined the effect of NO on JCl following either genetic ablation or chemical inhibition of transporters in the CCD. Since the application of hydrochlorothiazide (100 µM) or bafilomycin (5 nM) to the perfusate or ablation of the gene encoding pendrin did not alter NO-sensitive JCl, NO modulates JCl independent of the Naâº-dependent Clâ»/HCO3â» exchanger (NDCBE, Slc4a8), the A cell apical plasma membrane Hâº-ATPase and pendrin. In contrast, both total and NO-sensitive JCl and VT were abolished with application of an epithelial Na(+) channel (ENaC) inhibitor (3 µM benzamil) to the perfusate. We conclude that NO reduces Clâ» absorption in the CCD through a mechanism that is ENaC-dependent.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cloretos
/
Canais Epiteliais de Sódio
/
Túbulos Renais Coletores
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Assunto da revista:
FISIOLOGIA
/
NEFROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos