Development of Hypertension in a Rat Model of Diet-Induced Obesity

Abstract

Abstract-Although obesity is a risk factor for hypertension, the relationship between these 2 conditions is not well understood. Therefore, we examined some parameters of hypertension and cardiovascular disease in a dietary model of obesity. Male Sprague-Dawley rats were provided either a control diet (C) or a diet containing 32% kcal as fat (similar to a Western diet) for 1, 3, or 10 weeks. Rats in the latter group diverged based on body weight gain into obesity-prone (OP) and obesity-resistant (OR) groups. Systolic blood pressure in OP rats was significantly higher after 10 weeks of the diet (149Ϯ4.8 mm Hg) compared with both OR and C groups (131Ϯ3.7 and 129Ϯ4.5 mm Hg, respectively). The aortic wall area of OP rats was significantly increased, indicating arterial hypertrophy, and a 2-fold increase in plasma renin activity was found in OP rats compared with OR and C rats. The lipid profile showed a significant increase in plasma and VLDL triglycerides of OP versus OR and C groups as early as 3 weeks on the diet. Plasma and LDL-cholesterol levels were increased in the OP group versus the OR and C groups after 3 weeks of the diet, but the difference was blunted after 10 weeks. Lipid peroxidation (thiobarbituric acid-reactive substances) in OP rats was increased 2-fold in LDL and 1.5-fold in aortic wall compared with OR rats, suggesting an increased oxidative stress in these animals. Periodic acid-Schiff staining of the kidney showed mesangial expansion and focal sclerosis that were more prominent in OP rats than in OR rats. The results suggest that hypercholesterolemia, but not hypertriglyceridemia, is linked to the diet; that hypertension and renin-angiotensin system activation are associated with obesity; and that lipid peroxidation and renal damage are the results of both factors. (Hypertension. 2000;35:1009-1015.)besity is a complex, multifactorial disease that is often associated with diabetes, cardiovascular diseases, and stroke. Among other factors, obesity is an important contributor to essential hypertension in humans. Data from the Framingham Heart Study suggest that Ϸ78% of essential hypertension in men and Ϸ65% of essential hypertension in women can be directly attributed to obesity. 1 However, the mechanisms that link obesity with high blood pressure and altered renal function have not been fully elucidated. One problem in the study of the mechanisms of obesity hypertension has been the lack of a suitable animal model. The ideal model would not only have the features of human hypertension but also allow the study of sequential changes in cardiovascular and kidney function that occur with weight gain. The genetic models of obesity may or may not develop hypertension or do not mimic the changes observed in humans. For example, Zucker rats have decreased plasma renin activity (PRA) 2 as opposed to the high PRA observed in humans. 3 In contrast, diet-induced obese animal models appear to be the most relevant with regard to human obesity. Some of these models, such as the obese dog 4 or obese rabbit 5 fed...

Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

“…Adjustment of litter size or, more to the point, adjustment of early feeding patterns can influence adult blood pressure (42,45), as can the type of diet (13). In the current study, we also observed an increase in blood pressure as animals fed the high-fat diet gained weight.…”

Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation

“…25 Therefore, in this study, we decided to test whether blood pressure, measured in freely moving obesity-prone rats, can be increased by a diet with higher fat content (60% of total calorie), fed for a longer period (24 weeks) compared with the 32% HF diet fed for 10-12 weeks in earlier rat studies. [21][22][23] This diet treatment led to significantly elevated body weight and dyslipidemia; however, the plasma insulin and glucose levels were not elevated compared with chow-fed rats. This could be because both our control and HF diet-fed rats were selectively bred obesity-prone rats that show signs of metabolic syndrome even when fed with regular chow.…”

“…20 However, HF feeding in rats led to mixed results. Although some studies reported significant increases in blood pressure using tail cuff measurements, 21,22 others that used telemetry showed no change. 23 In addition, the question was raised that higher blood pressure values measured with tail cuff in HFfed animals were the result of an augmented stress response to restraint accompanying this blood pressure measurement procedure.…”

Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotectic enzymes in humans

“…They include the activation of the renin -angiotensin system, 8,9 high levels of circulating leptin, 10 reduced growth hormone concentration, 11 and activation of the sympathetic nervous system. 12 Although animal studies in rats have shown that obesity is associated with increased myocardial oxidative stress 13 and increased lipid peroxidation, 14 to the best of our knowledge there is no report in the literature of the effect of obesity per se on lipid peroxidation and erythrocyte cytoprotection in humans.…”