Hormonal regulation of the human adipose-tissue renin–angiotensin system: relationship to obesity and hypertension

OBJECTIVE: Adipose tissue secretes vasoactive substances which may contribute to the development of obesity-related hypertension. The aim of this work was to study the expression of renin-angiotensin system genes in adipose tissue of obese hypertensive subjects and the hormonal regulation of these genes. DESIGN: Differential expression of renin-angiotensin system genes in subcutaneous abdominal adipocytes of 12 lean normotensive, eight obese normotensive, and 10 obese hypertensive women was determined in a cross-sectional study. In vitro hormonal regulation of these genes was studied in primary human adipocytes obtained by breast reduction from healthy women. METHODS: In the clinical study, 24-h ambulatory blood pressure measurement and anthropometry were used to characterize the volunteers, and adipocytes were obtained by subcutaneous needle biopsy. The in vitro regulation of renin-angiotensin system genes by hydrocortisone, insulin, thyroxin, estradiol and angiotensin II on primary cultured human mammary adipocytes was studied by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: While expression of the angiotensinogen gene was significantly lower in adipocytes from both obese groups, the renin, angiotensin-converting enzyme and angiotensin II type 1 receptor genes were significantly upregulated in obese hypertensives. Hydrocortisone increased angiotensin II type 1 receptor gene and protein expression in a time- and dose-dependent manner in human adipocytes, but had no significant influence on other renin-angiotensin system genes. Expression of these genes was not significantly affected by any of the other tested hormones. CONCLUSIONS: Renin-angiotensin system genes are differentially regulated in human obesity and hypertension. The role of the adipose-tissue renin-angiotensin system in the development of obesity-associated hypertension or metabolic disease clearly warrants further study.