Submitted on April 23, 2007
Accepted on June 13, 2007
Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury
Jane Stubbe1, Kirsten Madsen1, Finn T Nielsen1, Rasmus K Bonde2, Ole Skott3, and Boye L. Jensen4*
1 Physiology and Pharmacology, University of Southern Denmark, Denmark
2 Physiology and Pharmacology, University of Southen Denmark, Denmark
3 Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark
4 Physiology and Pharmacology, University of Southern Denmark, Odense C, Denmark
* To whom correspondence should be addressed. E-mail: bljensen{at}health.sdu.dk.
We hypothesized that aldosterone promotes development of the renal medulla in the postnatal period and that COX-2 activity contributes to renal dysfunction after impaired aldosterone signalling. To test the 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 medullary interstitial osmolality was lower in the ADX group while COX-2 and PGE2 tissue levels were significantly elevated compared to sham. Substitution with DOCA and corticosterone corrected these changes, while 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/day, day 17-20) increased weight gain, urinary concentrating ability and papillary osmolality. After fluid deprivation, parecoxib attenuated weight loss and increase in plasma [Na+] 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.
