Weight Loss and the Renin-Angiotensin-Aldosterone System

[Guest guest]

FYI:

2005 American Heart Association, Inc.

Volume 45(3) March 2005 pp 356-363

Weight Loss and the Renin-Angiotensin-Aldosterone System

Abstract—

The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on the circulating and adipose tissue renin-angiotensin-aldosterone system in menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, and angiotensin II. In adipose tissue biopsy samples, we analyzed angiotensinogen, renin, renin-receptor, angiotensin-converting enzyme, and angiotensin II type-1 receptor gene expression. Obese women (n=19) had higher circulating angiotensinogen, renin, aldosterone, and angiotensin-converting enzyme than lean women (n=19), and lower angiotensinogen gene expression in adipose tissue. Seventeen women successfully participated in a weight reduction protocol over 13 weeks to reduce daily caloric intake by 600 kcal. Body weight was reduced by -5%, as were angiotensinogen levels by -27%, renin by -43%, aldosterone by -31%, angiotensin-converting enzyme activity by -12%, and angiotensinogen expression by -20% in adipose tissue (all P<0.05). The plasma angiotensinogen decrease was highly correlated with the waist circumference decline (r=0.74; P<0.001). Weight and renin-angiotensin-aldosterone system reductions were accompanied by a -7-mm Hg reduced systolic ambulatory blood pressure. These data suggest that a 5% reduction in body weight can lead to a meaningfully reduced renin-angiotensin-aldosterone system in plasma and adipose tissue, which may contribute to the reduced blood pressure.

Obesity leads to hypertension and increased cardiovascular risk.1,2 The renin-angiotensin-aldosterone system (RAAS) has been implicated by several authors.3 In humans, increased circulating angiotensinogen (AGT), renin, aldosterone, and angiotensin-converting enzyme (ACE) activity were reported in obese subjects.4–10 Furthermore, increased RAAS gene expression was described in adipose tissue, especially in rodent models of obesity.3,11–15 The link between adipose tissue AGT gene expression and blood pressure was recently documented in 2 mouse models. Targeted AGT expression in adipocytes of wild-type and AGT knockout mice increased circulating AGT levels and blood pressure.16 Targeted expression of 11[beta]-hydroxysteroid dehydrogenase-1 in adipocytes increased blood pressure, plasma AGT, and adipose tissue AGT gene expression in mice with a wild-type genetic background.17,18 The relationship between blood pressure and the RAAS in obese humans comes mostly from observational and not from intervention studies. The influence of weight loss on RAAS activity, especially on AGT plasma levels and the adipose tissue RAAS, has not been explored.

regards.