title: AT1-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity.
abstract: Previous studies in our laboratory demonstrated that rats exhibiting obesity in response to a moderately high-fat (MHF) diet developed hypertension associated with activation of the local and systemic renin-angiotensin system. In this study, we examined the effect of the angiotensin type 1 (AT(1))-receptor antagonist, losartan, on blood pressure in obesity-prone (OP) and obesity-resistant (OR) rats fed a MHF diet. Using telemetry monitoring, we characterized the evolution of blood pressure elevations during the development of obesity. Male Sprague-Dawley rats were implanted with telemetry transducers for chronic monitoring of blood pressure, and baseline measurements were obtained. Rats were then switched to the MHF diet (32% kcal as fat) and were segregated into OP and OR groups at week 5. At week 9 on the MHF diet, OP rats exhibited significantly greater 24-h mean arterial blood pressure compared with OR rats (OP: 105 +/- 4 mmHg, OR: 96 +/- 2 mmHg; P < 0.05). Elevations in blood pressure in OP rats were manifest as an increase in systolic pressure. Administration of losartan to all rats at week 9 resulted in a reduction in blood pressure; however, losartan had the greatest effect in OP rats (percent decrease in mean arterial pressure by losartan; OP: 19 +/- 4, OR: 10 +/- 2%; P < 0.05). These results demonstrate that elevations in blood pressure occur subsequent to established obesity in rats fed a high-fat diet. Moreover, these results demonstrate the ability of losartan to reverse the blood pressure increase from diet-induced obesity, supporting a primary role for the renin-angiotensin system in obesity-associated hypertension.
authors.affiliation: Division of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0200, USA.
authors.forename: Carine M
authors.initials: CM
authors.lastname: Boustany
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
authors.forename: David C
authors.initials: DC
authors.lastname: Randall
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage*; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000209:etiology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004041:Dietary Fats; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan