Although obesity is a known risk factor for the development of hypertension, the mechanisms by which obesity increase the risk for hypertension are poorly understood. It has been proposed that the hyperinsulinemia/insulin resistance associated with obesity contributes to the development of hypertension by stimulating the sympathetic nervous system, increasing renal sodium reabsorption, and increasing peripheral vascular resistance. Alterations in these systems have not been characterized in animal models of obesity-related hypertension. The long-term objective of this application is to understand the mechanisms which produce hypertension in obesity.
The specific aims of this application are: 1. To examine and characterize the relationship between hyperinsulinemia/insulin resistance and blood pressure in canine and rodent models of hypertension. 2. To determine if variable insulin sensitivity of the systems which are thought to cause insulin dependent hypertension explains the variable blood pressure response to obesity. 3. To study changes in renal function, sympathetic nervous system and regional vascular resistance in animal models of obesity-associated hypertension. 4. To assess the role of high versus low saturated fat diet in the expression of dietary obesity and hypertension. These studies will be completed in the whole animal. Sensitivity of muscle to insulin stimulated glucose disposal, of kidney to insulin stimulated sodium reabsorption and of the sympathetic nervous system to insulin stimulation will be assessed using a hyperinsulinemic clamp. Renal function will be assessed by measuring electrolyte excretion under icontrolled conditions. SNS activity will be assessed by measuring circulating catecholamines. Cardiovascular function and regional vascular resistance will be ,assessed by the radioactive microsphere technique.
| Borne, A T; Wolfsheimer, K J; Truett, A A et al. (1996) Differential metabolic effects of energy restriction in dogs using diets varying in fat and fiber content. Obes Res 4:337-45 |
