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Although the relationship between an increase in adipose tissue and a rise in blood pressure has long been recognized, the mechanism linking these two phenomena has yet to be fully understood. Recently, it has become evident that adipose tissue is a rich source of metabolically active molecules, including free fatty acids, leptin and angiotensinogen, the precursor of angiotensin II. The latter finding has prompted speculation on the possible role of adipocyte-derived angiotensinogen in the relationship between body weight and blood pressure. Therefore we examined the relationship between blood pressure, angiotensinogen, body mass index (BMI) and leptin levels in healthy normotensive subjects who are genetically predisposed to the development of hypertension.We studied 40 subjects with a positive family history of hypertension and 51 subjects with a negative family history. After the blood pressure measurements, blood samples were collected for the assessment of angiotensinogen, leptin, glucose, insulin, renin activity and electrolytes. Oral glucose tolerance was studied by an oral glucose tolerance test (75 g glucose).Plasma angiotensinogen was significantly correlated with both BMI (r = 0.29, P < 0.01) and plasma leptin (r = 0.40, P < 0.001). While plasma angiotensinogen and blood pressure were positively correlated only in subjects with a positive family history of hypertension (r = 0.33, P < 0.05), plasma leptin was related to blood pressure in both groups (r = 0.26, P = 0.01). Furthermore, the insulin response to an oral glucose load was significantly related to both plasma angiotensinogen (r = 0.22, P < 0.05) and plasma leptin (r = 0.47, P < 0.001).These findings support the hypothesis that circulating angiotensinogen levels are related to adipose mass in young, normotensive, nonobese men. Further studies on the relationship between adipose tissue and systemic or local renin-angiotensin systems appear warranted.