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

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Abstract
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. 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. 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). 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. 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.