Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury.

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Resumé

 
Udgivelsesdato: 2007-Sep
OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Renal Physiology
Vol/bind293
Udgave nummer3
Sider (fra-til)F780-F789
Antal sider10
ISSN0363-6127
DOI
StatusUdgivet - 1. sep. 2007

Fingeraftryk

Adrenalectomy
Desoxycorticosterone Acetate
Kidney
Mineralocorticoids
Wounds and Injuries
Aldosterone
Weight Gain
Kidney Concentrating Ability
Cyclooxygenase 2 Inhibitors
Dinoprostone
parecoxib

Citer dette

@article{409f4d90ce3611dc8674000ea68e967b,
title = "Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury.",
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 PGE2 tissue 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 = "Adrenal Glands, Adrenalectomy, Aldosterone, Animals, Corticosterone, Cyclooxygenase 2, Cyclooxygenase Inhibitors, Female, Isoxazoles, Kidney Medulla, Male, Rats, Rats, Sprague-Dawley, Sodium Chloride, Urine, Weight Gain",
author = "Jane Stubbe and Kirsten Madsen and Nielsen, {Finn T} and Bonde, {Rasmus K} and Ole Sk{\o}tt and Jensen, {Boye L}",
year = "2007",
month = "9",
day = "1",
doi = "10.1152/ajprenal.00193.2007",
language = "English",
volume = "293",
pages = "F780--F789",
journal = "American Journal of Physiology: Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury.

AU - Stubbe, Jane

AU - Madsen, Kirsten

AU - Nielsen, Finn T

AU - Bonde, Rasmus K

AU - Skøtt, Ole

AU - Jensen, Boye L

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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 PGE2 tissue 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.

AB - 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 PGE2 tissue 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.

KW - Adrenal Glands

KW - Adrenalectomy

KW - Aldosterone

KW - Animals

KW - Corticosterone

KW - Cyclooxygenase 2

KW - Cyclooxygenase Inhibitors

KW - Female

KW - Isoxazoles

KW - Kidney Medulla

KW - Male

KW - Rats

KW - Rats, Sprague-Dawley

KW - Sodium Chloride

KW - Urine

KW - Weight Gain

U2 - 10.1152/ajprenal.00193.2007

DO - 10.1152/ajprenal.00193.2007

M3 - Journal article

VL - 293

SP - F780-F789

JO - American Journal of Physiology: Renal Physiology

JF - American Journal of Physiology: Renal Physiology

SN - 1931-857X

IS - 3

ER -