Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity. Carroll, Joan F., Terry M. Dwyer, Andrew W. Grady, Glenn A. Reinhart, Jean-Pierre Montani, Kathy Cockrell, Edward F. Meydrech, and H. Leland Mizelle. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216 -4505
APStracts 3:0062H, 1996.
Although obesity is a major risk factor for morbidity and mortality, the mechanisms mediating cardiovascular abnormalities in response to weight gain are unclear. One reason for the paucity of information in this area is the lack of appropriate animal models for the study of human obesity. Therefore, the goal of the present study was to develop a small animal model of dietary-induced obesity that mimics many of the characteristics of human obesity. We studied female New Zealand White rabbits fed either a normal (n=17) or high fat diet (n=15) and examined the cardiovascular consequences of obesity including changes in blood pressure, humoral activation, and end organ effects such as cardiac hypertrophy. After 12 weeks, rabbits on the high fat diet were 46% heavier than their lean counterparts (5.49+/-0.09 vs 3.77+/-0.06 kg, respectively; p=0.0001). Obese rabbits had higher resting heart rates than lean rabbits (220+/-7 vs 177+/-6 b/min; p=0.0001), and developed hypertension (96+/-2 vs 85+/ -1 mm Hg; p=0.0001), hyperinsulinemia (32.5+/-3.4 vs 15.5+1.0 [mu]U/ml; p=0.0001), hyperglycemia (162.4+/-2.9 vs 141.9+/-2.7 mg/dl; p=0.0001), and elevated triglycerides (102.3+/-9.1 vs 48.5+/-4.0 mg/dl; p=0.0001). Obese rabbits also developed cardiac hypertrophy as evidenced by left ventricular (LV) dry weights that were 52% greater in obese than in lean rabbits (p=0.0003). In addition, LV total protein was increased in proportion to the increase in LV weight. The results of this study suggest that rabbits fed a high fat diet for a period of 12 weeks develop many of the characteristics of human obesity. The obese rabbit should provide a small and relatively inexpensive animal model to investigate mechanisms of obesity-related cardiovascular abnormalities.

Received 15 September 1995; accepted in final form 14 December
1995.
APS Manuscript Number H871-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96