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KMID : 1102220220410060699
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Kidney Research and Clinical Practice
2022 Volume.41 No. 6 p.699 ~ p.706
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Nitric oxide-inhibited chloride transport in cortical thick ascending limbs is reversed by 8-iso-prostaglandin-F2α
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Pablo D. Cabral
Guillermo B. Silva
Sandra T. Baigorria
Luis I. Juncos
Ebenezer I. O. Ajayi
Nestor H. Garcia
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Abstract
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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 (JCl) 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 JCl by decreasing cAMP bioavailability, we measured 8-iso-PGF2α-stimulated cAMP in the presence of sodium nitroprusside (SNP).
Results: The NO donor, SNP (10-6 M), decreased JCl by 41%, while luminal 8-iso-PGF2α (100 μM) increased JCl to 315 ± 46 pmol/min/mm (p < 0.003), reversing the effects of the NO donor. SNP inhibited JCl, 8-iso-PGF2α failed to increase JCl 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 JCl in the cTAL can be reversed by 8-iso-PGF2α, 2) 8-iso-PGF2α and NO interaction requires PKA to control JCl, and 3) in the presence of NO, 8-iso-PGF2α continues to stimulate JCl because NO cannot reverse 8-iso-PGF2α-stimulated cAMP level.
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KEYWORD
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Hypertension, Isoprostanes, Nitric oxide, Oxidative stress
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