Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury
Open Access
- 1 September 2007
- journal article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 293 (3), F780-F789
- https://doi.org/10.1152/ajprenal.00193.2007
Abstract
We hypothesized that aldosterone promotes development of the renal medulla in the postnatal period and that cyclooxygenase-2 (COX-2) activity contributes to renal dysfunction after impaired aldosterone signaling. To test these hypotheses, rat pups underwent either sham operation or adrenalectomy at postnatal day 10. Adrenalectomized rats were divided into no steroid substitution (ADX), corticosterone replacement (ADX-C), and corticosterone and DOCA substitution (ADX-CD) groups that received subcutaneous pellets with steroids. Without replacement, pups failed to thrive and exhibited impaired urinary-concentrating ability. The renal medulla was significantly smaller, and the medullary interstitial osmolality was lower in the ADX group, whereas COX-2 and PGE2tissue levels were significantly elevated compared with levels shown in sham animals. Substitution with DOCA and corticosterone corrected these changes, whereas corticosterone replacement alone improved survival but not weight gain and urinary-concentrating ability. Administration of a COX-2 inhibitor to ADX rats (parecoxib, 5 mg·kg−1·day−1, days 17–20) increased weight gain, urinary-concentrating ability, and papillary osmolality. After fluid deprivation, parecoxib attenuated weight loss and the increase in plasma Na+concentration and osmolality. It is concluded that mineralocorticoid is required for normal postnatal development of the renal medulla. COX-2 contributes to impaired urine-concentrating ability, NaCl loss, and extracellular volume depletion in postnatal mineralocorticoid deficiency.Keywords
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