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This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/R181    most recent 00507.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Boustany, C. M Articles by Cassis, L. A Search for Related Content PubMed PubMed Citation Articles by Boustany, C. M Articles by Cassis, L. A

NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

AT₁-receptor antagonism reverses the blood pressure elevation associated with diet-induced obesity

¹Division of Pharmaceutical Sciences, ²Graduate Center for Biomedical Engineering, ³Department of Physiology, ⁴Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky

Submitted 28 July 2004 ; accepted in final form 7 March 2005

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 (AT₁)-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.

angiotensin II; obesity-induced hypertension

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