| First Author | Slattery P | Year | 2017 |
| Journal | Am J Physiol Renal Physiol | Volume | 312 |
| Issue | 6 | Pages | F1044-F1055 |
| PubMed ID | 28274925 | Mgi Jnum | J:280672 |
| Mgi Id | MGI:6368980 | Doi | 10.1152/ajprenal.00565.2016 |
| Citation | Slattery P, et al. (2017) Salt supplementation ameliorates developmental kidney defects in COX-2(-/-) mice. Am J Physiol Renal Physiol 312(6):F1044-F1055 |
| abstractText | Deficiency of cyclooxygenase-2 (COX-2) activity in the early postnatal period causes impairment of kidney development leading to kidney insufficiency. We hypothesize that impaired NaCl reabsorption during the first days of life is a substantial cause for nephrogenic defects observed in COX-2(-/-) mice and that salt supplementation corrects these defects. Daily injections of NaCl (0.8 mg.g(-1).day(-1)) for the first 10 days after birth ameliorated impaired kidney development in COX-2(-/-) pups resulting in an increase in glomerular size and fewer immature superficial glomeruli. However, impaired renal subcortical growth was not corrected. Increasing renal tubular flow by volume load or injections of KCl did not relieve the renal histomorphological damage. Administration of torsemide and spironolactone also affected nephrogenesis resulting in diminished glomeruli and cortical thinning. Treatment of COX-2(-/-) pups with NaCl/DOCA caused a stronger mitigation of glomerular size and induced a slight but significant growth of cortical tissue mass. After birth, renal mRNA expression of NHE3, NKCC2, ROMK, NCCT, ENaC, and Na(+)/K(+)-ATPase increased relative to postnatal day 2 in wild-type mice. However, in COX-2(-/-) mice, a significantly lower expression was observed for NCCT, whereas NaCl/DOCA treatment significantly increased NHE3 and ROMK expression. Long-term effects of postnatal NaCl/DOCA injections indicate improved kidney function with normalization of pathologically enhanced creatinine and urea plasma levels; also, albumin excretion was observed. In summary, we present evidence that salt supplementation during the COX-2-dependent time frame of nephrogenesis partly reverses renal morphological defects in COX-2(-/-) mice and improves kidney function. |
