Endogenous nitric oxide inhibits chloride transport in the thick ascending limb.

Abstract

Nitric oxide (NO) inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (TALH) expresses NO synthase (NOS). However, the effects of NO on TALH transport have not been extensively studied. We hypothesized that endogenously produced NO directly decreases NaCl transport by the TALH. We first determined the effect of exogenously added NO on net chloride flux (JCl). The NO donor spermine NONOate (SPM; 10 microM) decreased JCl from 101.2 +/- 9.6 to 65.0 +/- 7.7 pmol. mm-1. min-1, a reduction of 35.5 +/- 6.4%, whereas controls did not decrease over time. To determine whether endogenous NO affects cortical TALH transport, we measured the effect of adding the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the substrate L-arginine (L-Arg), or its enantiomer D-arginine (D-Arg) on JCl. L-NAME and D-Arg did not alter JCl; in contrast, addition of 0.5 mM L-Arg decreased JCl by 40.2 +/- 10.4% from control. The inhibition of chloride flux by 0.5 mM L-Arg was abolished by pretreatment with L-NAME, indicating that cortical TALH NOS is active, but production of NO is substrate-limited in our preparation. Furthermore, cortical TALH chloride flux increased following removal of 0.5 mM L-Arg from the bath, indicating that the reductions in chloride flux observed in response to L-Arg are not the result of NO-mediated cytotoxicity. We conclude that 1) exogenous NO decreases cortical TALH JCl; 2) cortical TALHs produce NO in the presence of L-Arg, which decreases JCl; and 3) the response of cortical TALHs to L-Arg is reversible in vitro. These data suggest an important role for locally produced NO, which may act via an autocrine mechanism to directly affect TALH sodium chloride transport. Thus TALH NO synthesis and inhibition of chloride transport may contribute to the diuretic and natriuretic effects of NO observed in vivo.

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@article{Plato1999EndogenousNO, title={Endogenous nitric oxide inhibits chloride transport in the thick ascending limb.}, author={Craig F. Plato and Barbara A . Stoos and Danke Wang and Jeffrey L. Garvin}, journal={The American journal of physiology}, year={1999}, volume={276 1 Pt 2}, pages={F159-63} }