Abstract P193: Upregulation of Brain Renin-angiotensin System and Inflammation Mediates Leptin Sensitization of Angiotensin Ii-induced Hypertension
Leptin, an adipocyte-derived hormone, contributes to the increase in blood pressure (BP) associated with obesity. Obesity has also been shown to promote the renin-angiotensin system (RAS) activity and inflammation in the hypothalamus that increase BP and sympathetic activity. Our previous studies using an Induction-Delay-Expression experimental design demonstrated that a central leptin pretreatment resulted in an enhanced hypertensive response to subsequent treatment with angiotensin (ANG) II. The present study tested whether this central leptin sensitization of ANG II-induced hypertension is mediated by an increase in RAS acitivity and inflammation in the brain. Male rats prepared for telemetry BP recording and were pretreated during Induction with central leptin (20 ng/kg/min, ICV) alone or with either ANG II type 1 receptor (AT1R) antagonist irbesartan (125 μg/d) or the TNF-α synthesis inhibitor pentoxifylline (10 μg/h) for one week. After one week Delay, rats were treated during Expression with subcutaneous ANG II (120 ng/kg/min) for 2 weeks. The animals pretreated with central leptin responded with enhanced hypertension to ANG II ([[Unable to Display Character: ∆]]39.3±3.8 mmHg vs. [[Unable to Display Character: ∆]]21.2±5.2 mmHg). Central infusion of pentoxifylline or irbesartan during Induction blocked the sensitization produced by central leptin. RT-PCR analysis of tissue from the lamina terminalis indicated that leptin up-regulated mRNA expression of several components of the RAS and proinflammatory cytokines including AT1R, angiotensin converting enzyme, TNF-α and interleukin 1β. The results indicate that leptin-induced sensitization of ANG II-elicited hypertension is mediated by upregulation of central RAS and proinflammatory cytokines.
Author Disclosures: B. Xue: None. Y. Yu: None. F. Guo: None. T.G. Beltz: None. R.B. Felder: None. A.K. Johnson: None.
- © 2015 by American Heart Association, Inc.