title: The development of hypertension and hyperaldosteronism in a rodent model of life-long obesity.
abstract: Aldosterone has been linked to the deleterious cardiovascular effects of obesity in humans. The association of aldosterone with obesity in rodents is less well defined, particularly in models of diet-induced obesity. We hypothesized that adrenal aldosterone production and aldosterone synthase expression would be increased in rats with obesity-induced hypertension. Male Sprague Dawley rats were fed a high-fat (HF: 36% fat) or control diet from 3 wk of age, and mean arterial pressure (MAP) was measured by telemetry. MAP was increased after 4 wk of HF diet; this was 6 wk before changes in body weight. Mineralocorticoid receptor antagonism did not prevent the HF-induced increase in MAP. After 17 wk on the diets, HF rats had increased body and fat weights (abdominal and epididymal) and were insulin resistant (Homeostasis Model Assessment index: 3.53 ± 0.43 vs. 8.52 ± 1.77; control vs. HF, P < 0.05). Plasma aldosterone levels were increased in the HF rats (64.14 ± 14.96 vs. 206.25 ± 47.55 pg/ml; control vs. HF, P < 0.05). This occurred independently of plasma renin activity (4.8 ± 0.92 vs. 4.73 ± 0.66 ng/ml/h, control vs. HF). The increase in aldosterone was accompanied by a 2-fold increase in adrenal aldosterone synthase mRNA expression and zona glomerulosa hypertrophy. Rats were also studied after 8 wk of HF diet, a time when MAP, but not body weight, was increased. At this time plasma aldosterone was unchanged but plasma renin activity was increased (4.4 ± 0.5 vs. 8.1 ± 1.3 ng/ml/h; control vs. HF, P < 0.05). These studies suggest that rats fed a HF diet from weaning may be a useful model for studying obesity-associated hyperaldosteronism.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Northcott
authors.forename: Greg D
authors.initials: GD
authors.lastname: Fink
authors.forename: Hannah
authors.initials: H
authors.lastname: Garver
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Haywood
authors.forename: Erinn L
authors.initials: EL
authors.lastname: Laimon-Thomson
authors.forename: Jonathon L
authors.initials: JL
authors.lastname: McClain
authors.forename: Paulo W
authors.initials: PW
authors.lastname: Pires
authors.forename: William E
authors.initials: WE
authors.lastname: Rainey
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rigsby
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dorrance
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D006929:Hyperaldosteronism / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D004041:Dietary Fats; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2