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...

Colchicine has multiple mechanisms of action that affect inflammatory processes and result in its utility for treating and preventing acute gout flare. Other chronic inflammatory diseases that invoke these molecular pathways may represent new therapeutic applications for colchicine.

Abstract-The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (nϭ60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158Ϯ3.4 mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8Ϯ3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive substances showed a significant increase in the LDL fraction of OP rats (2.8Ϯ0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9Ϯ0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid-reactive substances showed a significant (3-and 5-fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition, free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptasepolymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/␤-actin ratio 1.3Ϯ0.04 in OP rats versus 0.44Ϯ0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress. Key Words: diet Ⅲ nitric oxide Ⅲ obesity Ⅲ oxidative stress Ⅲ kidney Ⅲ lipids O besity 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% in women can be directly attributed to obesity. 1 However, the mechanisms that link obesity with high blood pressure (BP) have not been fully elucidated. There are data that indicate increased oxidative stress in human essential hypertension 2,3 as well as in obese hypertensive patients. 4 Also, the involvement of the superoxide radical in BP regulation has been reported for several animal models of hypertension, such as the spontaneously hypertensive rat, 5,6 Dahl rat, 7 and angiotensin II-infused rat. 8 Romero's group (Haas et al 9 and Reckelhoff et al 10 ) has recently reported that subpressor doses of angiotensin II are able to generate oxidative stress in pigs and rats, which, in turn, is able to induce chronic elevations in BP. The increase in superoxide production in hypertension has been shown to have an impact ...

A purified moderately high fat diet has been developed to examine diet-induced obesity in rats. Male Sprague-Dawley rats were fed this or an AIN-76A diet for 15 wk and energy metabolism indices were monitored. Food intake, body weight and water balance indices were recorded on a weekly or daily basis. Over the 15-wk period, rats fed the experimental diet diverged into two groups differing in the rate of body weight gain. Animals were labeled as "gainers" or "resisters" depending on their susceptibility to obesity. Following the dietary period, rats were decapitated and trunk blood was collected for glucose and insulin measurements. Gainers consumed slightly more energy than resisters over the experimental period (P < 0.05), but due to greater fecal energy loss, absorbed energy did not differ. Hence gainers became obese without significantly altered energy retention. Urinary creatinine, urea nitrogen and water balance were not different between the groups and consequently could not explain body weight differences. Further, gainers had significantly greater plasma glucose concentration than controls, indicating a potential for these animals to become diabetic. Results suggest metabolic differences must account for the divergence in weight gain observed in the two groups. The dietary model characterized in this study should provide a useful tool to study diet-induced obesity and to determine its underlying mechanism.

The application of a human somatomedin-C radioimmunoassay for the determination of somatomedin-C in chicken plasma has been examined. Parallel inhibition of binding of 125I-labelled somatomedin-C to antisera raised against somatomedin-C was observed with acid-treated human and chicken plasma. The concentration of immunoreactive (IR)-somatomedin-C in the plasma of the domestic fowl appears to be GH dependent. Plasma concentrations of IR-somatomedin-C were reduced after hypophysectomy and partially restored by replacement therapy with chicken GH. The age/development pattern of circulating concentrations of IR-somatomedin-C has been determined in normal and dwarf strains of domestic fowl. Increases in the plasma concentration of IR-somatomedin-C were observed between 1 and 6 weeks of age in control male domestic fowl of either heavy (broiler type) or light (White Leghorn) strains. Thereafter, the plasma concentrations of IR-somatomedin-C remained constant in the heavy strain birds but declined in White Leghorn chicks. Plasma concentrations of IR-somatomedin-C were reduced in sex-linked dwarf chickens, in both light and heavy strains of fowl, but were unaffected in autosomal dwarf chickens.