Journal
HYPERTENSION
Volume 60, Issue 6, Pages 1524-U382Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.112.192690
Keywords
obesity; angiotensinogen; angiotensins; hypertension; adipose tissue
Categories
Funding
- National Heart, Lung, and Blood Institute [HL73085, HL62846, T32HL091812]
- National Center for Research Resources [P20RR021954]
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Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 +/- 3 versus 128 +/- 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 +/- 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit an increase in systolic blood pressure (126 +/- 2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agt(fl/fl) mice (low fat, 32 +/- 14; high fat, 219 +/- 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 +/- 7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat-and high fat-fed Agt(aP2) mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension. (Hypertension. 2012;60:1524-1530.)
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