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Kidney Res Clin Pract


Background: Salt reabsorption in the cortical thick ascending limb (cTAL) is regulated by opposing effects. Thus, while nitric oxide (NO) inhibits sodium chloride (NaCl) reabsorption, 8-iso-prostaglandin-F2α (8-iso-PGF2α) stimulates it. Their interaction, however, 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. We also evaluated whether 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: Basal JCl was 274 ± 85 pmol/min/mm. The NO donor, SNP (10-6 M), decreased JCl by 41% (333.5 ± 35.2 pmol/min/mm vs. 195.9 ± 26.1 pmol/min/mm), while 8-iso-PGF2α (100 μM) increased JCl to 315 ± 46 pmol/min/mm (p < 0.01), reversing the effects of the NO donor. While SNP inhibited JCl, 8-iso-PGF2α failed to increase JCl in the presence of H89. Basal cAMP was 56.3 ± 13.1 fmol/min/mm, that in the presence of the NO donor was 57.8 ± 6.1 fmol/min/mm, and that with 8-iso-PGF2α increased it to 92.1 ± 2.9 fmol/min/mm (n = 10, 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 in this nephron segment, 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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ePub ahead of print



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