Nitric oxide reduces Cl⁻ absorption in the mouse cortical collecting duct through an ENaC-dependent mechanism.

Pech V, Thumova M, Dikalov SI, Hummler E, Rossier BC, Harrison DG, Wall SM
Am J Physiol Renal Physiol. 2013 304 (11): F1390-7

PMID: 23515718 · PMCID: PMC3680692 · DOI:10.1152/ajprenal.00292.2012

Since nitric oxide (NO) participates in the renal regulation of blood pressure, in part, by modulating transport of Na⁺ and Cl⁻ in the kidney, we asked whether NO regulates net Cl⁻ flux (JCl) in the cortical collecting duct (CCD) and determined the transporter(s) that mediate NO-sensitive Cl⁻ absorption. Cl⁻ 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 Na⁺-dependent Cl⁻/HCO₃⁻ exchanger (NDCBE, Slc4a8), the A cell apical plasma membrane H⁺-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 Cl⁻ absorption in the CCD through a mechanism that is ENaC-dependent.

MeSH Terms (21)

Absorption Aldosterone Amiloride Angiotensin II Animals Anion Transport Proteins Chloride-Bicarbonate Antiporters Chlorides Epithelial Sodium Channels Female In Vitro Techniques Kidney Tubules, Collecting Male Mice Mice, Knockout NG-Nitroarginine Methyl Ester Nitric Oxide Nitric Oxide Donors Nitric Oxide Synthase Sodium Sulfate Transporters

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