Increased sensitivity of the obese Zucker rat to deoxycorticosterone-salt-induced hypertension.
OBJECTIVE
The objective of this study was to test the hypothesis that obesity increases the sensitivity of rats to experimentally induced hypertension.


METHODS
To induce hypertension, unilaterally nephrectomized lean and obese Zucker rats were injected with 25 mg/kg of deoxycorticosterone acetate (DOCA) twice weekly for 5 weeks and given water containing 1% NaCl to drink. Unilaterally nephrectomized control rats were injected with vehicle and drank tap water. Systolic blood pressure (SBP) was measured by the tail cuff method. Renal histology and urinary albumin excretion were used to assess the effects of the experimental treatment on the kidney.


RESULTS
Obese rats exhibited a significant rise in SBP at 4 days after the start of DOCA-salt treatment. In contrast, SBP of DOCA-treated lean rats was not significantly elevated from pretreatment measurements until day 22. Moreover, SBP was significantly higher during the plateau phase of blood pressure development in obese DOCA-salt treated rats (196 mmHg) than in correspondingly treated lean rats (150 mmHg). Both obesity and DOCA-salt treatment promoted glomerulosclerosis and mild tubulointerstitial damage in the kidney with DOCA-salt treatment exacerbating the effect of obesity. Urinary albumin excretion was significantly greater in obese control rats compared with lean controls and in DOCA-treated obese rats relative to vehicle-treated obese rats.


CONCLUSIONS
Results of this study indicate that obese Zucker rats are more sensitive to mineralocorticoid-induced hypertension than lean rats. This study provides experimental evidence supporting the epidemiological findings that obesity is a risk factor for the development of hypertension.
Morrison
Ryan G
RG
Departments of Physiology, Pathology, Cardiovascular Services, Pharmacology, and Anatomy Cell and Neurobiology, Marshall University, Joan C. Edwards School of Medicine, 1542 Spring Valley Drive, Huntington, West Virginia 25704, USA.
Carpenter
A Betts
AB
Moore
Stephany K
SK
Mangiarua
Elsa I
EI
Valentovic
Monica A
MA
Walker
Ernest M
EM
Wehner
Paulette S
PS
Rhoten
William B
WB
Touchon
Robert C
RC
McCumbee
William D
WD
D000818:Animals; D001794:Blood Pressure; D003900:Desoxycorticosterone; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000453:epidemiology; D005260:Female; D006977:Hypertension, Renal / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D009392:Nephrectomy; D009765:Obesity / Q000453:epidemiology*; D051381:Rats; D011924:Rats, Zucker; D012307:Risk Factors; D017673:Sodium Chloride, Dietary
D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone