Obesity induced renal oxidative stress contributes to renal injury in salt-sensitive hypertension.
1. 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). 2. 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/micromol creatinine, respectively) and this elevation was further increased in the obese DOCA-salt treated mice (2430 +/- 312 pg/micromol 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 microg/day, respectively). 3. 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.
Quigley
Jeffrey E
JE
Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA.
Elmarakby
Ahmed A
AA
Knight
Sarah F
SF
Manhiani
Marlina M
MM
Stepp
David W
DW
Olearzcyk
Jeffrey J
JJ
Imig
John D
JD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017419:Potassium, Dietary / Q000633:toxicity*; D017673:Sodium Chloride, Dietary / Q000633:toxicity*
D017419:Potassium, Dietary; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone