| Autor: |
Wu, Peng, Gao, Zhongxiuzi, Ye, Shiwei, Qi, Zhi |
| Zdroj: |
American Journal of Physiology - Renal Physiology; April 2016, Vol. 310 Issue: 8 pF755-F762, 8p |
| Abstrakt: |
We used patch-clamp techniques to examine whether nitric oxide (NO) decreases NaCl reabsorption by suppressing basolateral 10-pS Cl−channels in the thick ascending limb (TAL). Both the NO synthase substrate l-arginine (l-Arg) and the NO donor S-nitroso-N-acetylpenicillamine significantly inhibited 10-pS Cl−channel activity in the TAL. The inhibitory effect of l-Arg on Cl−channels was completely abolished in the presence of the NO synthase inhibitor or NO scavenger. Moreover, inhibition of soluble guanylyl cyclase abrogated the effect of l-Arg on Cl−channels, whereas the cGMP analog 8-bromo-cGMP (8-BrcGMP) mimicked the effect of l-Arg and significantly decreased 10-pS Cl−channel activity, indicating that NO inhibits basolateral Cl−channels by increasing cGMP production. Furthermore, treatment of the TAL with a PKG inhibitor blocked the effect of l-Arg and 8-BrcGMP on Cl−channels, respectively. In contrast, a phosphodiesterase 2 inhibitor had no significant effect on l-Arg or 8-BrcGMP-induced inhibition of Cl−channels. Therefore, we conclude that NO decreases basolateral 10-pS Cl−channel activity through a cGMP-dependent PKG pathway, which may contribute to the natriuretic and diuretic effects of NO in vivo. |
| Databáze: |
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