IngentaConnect OBESITY INDUCED RENAL OXIDATIVE STRESS CONTRIBUTES TO RENAL INJUR...

Authors: Quigley, Jeffrey E; Elmarakby, Ahmed A; Knight, Sarah F; Manhiani, Marlina M; Stepp, David W; Olearzcyk, Jeffrey J; Imig, John D

Source: Clinical and Experimental Pharmacology and Physiology, Volume 36, Number 7, July 2009 , pp. 724-728(5)

Publisher: Blackwell Publishing

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Abstract:

SUMMARY

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In the present study, we determined the role of hypertension, oxidative stress and inflammation on kidney damage in a rodent model of obesity and diabetes. Hypertension was induced in male obese (db/db) mice and lean (db/m) mice by implantation of deoxycorticosterone acetate (DOCA) pellets and mice were allowed to drink water containing 1% salt. Mice were divided into six groups as follows: obese and lean control, obese and lean 1% salt (salt) and obese and lean DOCA plus 1% salt (DOCA-salt).

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Blood pressure was significantly increased in lean and obese DOCA-salt groups relative to their respective controls; however, there was no difference in blood pressure between the lean and obese control and salt groups. Urinary 8-isoprostane was increased in obese control compared with lean control mice (1464 ± 267 vs 493 ± 53 pg/µmol creatinine, respectively) and this elevation was further increased in the obese DOCA-salt treated mice (2430 ± 312 pg/µmol creatinine). Urinary monocyte chemoattractant protein-1 excretion and CD68-positive cells were also increased in both obese and lean DOCA-salt groups compared with their respective controls. Furthermore, DOCA-salt treatment increased collagen IV excretion in both obese and lean mice compared with controls, but there was no difference between obese and lean DOCA-salt groups. Urinary albumin excretion was significantly increased in the obese compared with the lean DOCA-salt mice (507 ± 160 vs 202 ± 48 µg/day, respectively).

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These data suggest that obese DOCA-salt hypertensive mice exhibit greater renal injury than lean DOCA-salt hypertensive mice in a manner independent of blood pressure and that this renal injury is associated with obesity related pre-existing renal oxidative stress.

OBESITY INDUCED RENAL OXIDATIVE STRESS CONTRIBUTES TO RENAL INJURY IN SALT-SENSITIVE HYPERTENSION