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      • SCOPUSKCI등재SCIE

        Nitric oxide-inhibited chloride transport in cortical thick ascending limbs is reversed by 8-iso-prostaglandin-F2α

        ( Pablo D. Cabral ),( Guillermo B. Silva ),( Sandra T. Baigorria ),( Luis I. Juncos ),( Ebenezer I. O. Ajayi ),( Néstor H. García ) 대한신장학회 2022 Kidney Research and Clinical Practice Vol.41 No.6

        Background: Sodium chloride (NaCl) reabsorption in the cortical thick ascending limb (cTAL) is regulated by opposing effects. Nitric oxide (NO) inhibits NaCl reabsorption while 8-iso-prostaglandin-F2α (8-iso-PGF2α) stimulates it. Their interaction has not been evaluated in the cTAL. Because 8-iso-PGF2α has considerable stability while NO is a free radical with a short half-life, we hypothesized that, in the cTAL, the inhibition of NaCl absorption will be reversed by 8-iso-PGF2α. Methods: Chloride absorption (J<sub>Cl</sub>) was measured in isolated perfused cTALs and whether the activation of protein kinase A (PKA) is required for this interaction. Since cyclic adenosine monophosphate (cAMP) is a major messenger for the 8-iso-PGF2α signaling cascade, and NO inhibits J<sub>Cl</sub> by decreasing cAMP bioavailability, we measured 8-iso-PGF2α-stimulated cAMP in the presence of sodium nitroprusside (SNP). Results: The NO donor, SNP (10<sup>-6</sup> M), decreased J<sub>Cl</sub> by 41%, while luminal 8-iso-PGF2α (100 μM) increased J<sub>Cl</sub> to 315 ± 46 pmol/ min/mm (p < 0.003), reversing the effects of the NO donor. SNP inhibited J<sub>Cl</sub>, 8-iso-PGF2α failed to increase J<sub>Cl</sub> in the presence of H89. Basal cAMP was 56 ± 13 fmol/min/mm, in the presence of SNP 57 ± 6 fmol/min/mm, and 8-iso-PGF2α increased it to 92 ± 2 fmol/min/mm (p < 0.04). Conclusion: We concluded that 1) NO-induced inhibition of J<sub>Cl</sub> in the cTAL can be reversed by 8-iso-PGF2α, 2) 8-iso-PGF2α and NO interaction requires PKA to control J<sub>Cl</sub>, and 3) in the presence of NO, 8-iso-PGF2α continues to stimulate J<sub>Cl</sub> because NO cannot reverse 8-iso-PGF2α-stimulated cAMP level.

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