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

Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R181-6. doi: 10.1152/ajpregu.00507.2004. Epub 2005 Mar 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Dietary Fats / administration & dosage*
  • Disease Susceptibility
  • Dose-Response Relationship, Drug
  • Losartan / pharmacology*
  • Male
  • Obesity / etiology*
  • Obesity / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Dietary Fats
  • Receptor, Angiotensin, Type 1
  • Losartan