Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2004-10, Vol.287 (4), p.R943-R949
• Main Authors: Boustany, Carine M, Bharadwaj, Kalyani, Daugherty, Alan, Brown, David R, Randall, David C, Cassis, Lisa A
• Format: Article
• Language: English
• Subjects: Adipose Tissue - physiopathology; Angiotensinogen - biosynthesis; Animals; Autoradiography; Blood Pressure - physiology; Cholesterol - blood; Diet; DNA Primers; Gene Expression Regulation - physiology; Hemodynamics - physiology; Hypertension - physiopathology; Male; Obesity - physiopathology; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin - physiology; Renin-Angiotensin System - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - isolation & purification; Weight Gain - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00265.2004

1 Division of Pharmaceutical Sciences, 2 Department of Internal Medicine, 3 Graduate Center for Nutritional Sciences, 4 Graduate Center for Biomedical Engineering, and 5 Department of Physiology, University of Kentucky, Lexington, Kentucky 40536 Submitted 23 April 2004 ; accepted in final form 3 June 2004 In obesity-related hypertension, activation of the renin-angiotensin system (RAS) has been reported despite marked fluid volume expansion. Adipose tissue expresses components of the RAS and is markedly expanded in obesity. This study evaluated changes in components of the adipose and systemic RAS in diet-induced obese hypertensive rats. RAS was quantified in adipose tissue and compared with primary sources for the circulating RAS. Male Sprague-Dawley rats were fed either a low-fat (LF; 11% kcal as fat) or moderately high-fat (32% kcal as fat) diet for 11 wk. After 8 wk, rats fed the moderately high-fat diet segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on their body weight gain (body weight: OR, 566 ± 10; OP, 702 ± 20 g; P < 0.05). Mean arterial blood pressure was increased in OP rats (LF: 97 ± 2; OR: 97 ± 2; OP: 105 ± 1 mmHg; P < 0.05). Quantification of mRNA expression by real-time PCR demonstrated a selective increase (2-fold) in angiotensinogen gene expression in retroperitoneal adipose tissue from OP vs. OR and LF rats. Similarly, plasma angiotensinogen concentration was increased in OP rats (LF: 390 ± 48; OR: 355 ± 24; OP: 530 ± 22 ng/ml; P < 0.05). In contrast, other components of the RAS were not altered in OP rats. Marked increases in the plasma concentrations of angiotensin peptides were observed in OP rats (angiotensin II: LF: 95 ± 31; OR: 59 ± 20; OP: 295 ± 118 pg/ml; P < 0.05). These results demonstrate increased activity of the adipose and systemic RAS in obesity-related hypertension. retroperitoneal adipose; mean arterial pressure; angiotensin II Address for reprint requests and other correspondence: L. A. Cassis, Professor and Director, Graduate Center for Nutritional Sciences, Rm. 521B, Charles T. Wethington Bldg., Univ. of Kentucky, Lexington, KY 40536-0200 (E-mail: lcassis{at}uky.edu )