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10.1152/ajprenal.00583.2014

http://scihub22266oqcxt.onion/10.1152/ajprenal.00583.2014
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suck abstract from ncbi


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pmid25503735      Am+J+Physiol+Renal+Physiol 2015 ; 308 (5): F444-9
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  • Endogenous flow-induced nitric oxide reduces superoxide-stimulated Na/H exchange activity via PKG in thick ascending limbs #MMPMID25503735
  • Hong NJ; Garvin JL
  • Am J Physiol Renal Physiol 2015[Mar]; 308 (5): F444-9 PMID25503735show ga
  • Luminal flow stimulates endogenous nitric oxide (NO) and superoxide (O2?) production by renal thick ascending limbs (TALs). The delicate balance between these two factors regulates Na transport in TALs; NO enhances natriuresis, whereas O2? augments Na absorption. Endogenous, flow-stimulated O2? enhances Na/H exchange (NHE). Flow-stimulated NO reduces flow-induced O2?, a process mediated by cGMP-dependent protein kinase (PKG). However, whether flow-stimulated, endogenously-produced NO diminishes O2?-stimulated NHE activity and the signaling pathway involved are unknown. We hypothesized that flow-induced NO reduces the stimulation of NHE activity caused by flow-induced O2? via PKG in TALs. Intracellular pH recovery after an acid load was measured as an indicator of NHE activity in isolated, perfused rat TALs. l-Arginine, the NO synthase substrate, decreased NHE activity by 34 ± 5% (n = 5; P < 0.04). The O2? scavenger tempol decreased NHE activity by 46 ± 8% (n = 6; P < 0.004) in the absence of NO. In the presence of l-arginine, the inhibitory effect of tempol on NHE activity was reduced to ?19 ± 6% (n = 6; P < 0.03). The soluble guanylate cyclase inhibitor LY-83583 blocked the effect of l-arginine thus restoring tempol's effect on NHE activity to ?42 ± 4% (n = 6; P < 0.0005). The PKG inhibitor KT-5823 also inhibited l-arginine's effect on tempol-reduced NHE activity (?43 ± 5%; n = 5; P < 0.03). We conclude that flow-induced NO reduces the stimulatory effect of endogenous, flow-induced O2? on NHE activity in TALs via an increase in cGMP and PKG activation.
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