Epidemiological studies have enumerated a host of variables that seem to play a role in the development of essential hypertension in humans, including genetics, high sodium intake, exercise (and its relationship to obesity), and societal stress. It has, of course, been difficult to determine precisely what role each of these variables plays in essential hypertension due to the presence of a mixture of variables within a given population or sub- population. It is even more difficult to study life-span changes in populations or to determine the mechanisms which relate genetic and environmental variables to chronic alterations in physiological and biochemical function. Animal models afford the opportunity to perform long-term studies in a short time, and thus offer a means to study the mechanisms by which genetic and environmental variables produce hypertension. While there has been an adequate genetic model for hypertension for a number of years (the spontaneously hypertensive rat, or SHR), there is no suitable animal model for studying the range of environmental variables thought to be related to the development of essential hypertension in humans. Our laboratory has recently developed such a model, which we call the borderline hypertensive rat (BHR). The BHR has one hypertensive and one normotensive parent. The mixed genetic background seems more relevant to human essential hypertension than previous models, which have focused on animals with long histories of normotension or hypertension. A number of hypotheses relating the interactions between dietary sodium intake, tail shock stress, exercise and genetic history of hypertension will be tested in animals - with either no parental history of hypertension (normotensive parents), a mixed parental history (BHR), or a strong parental history (SHR) - studied for 4, 8, or 16 months. The major dependent variables will assess CNS/renal interactions in the development of chronic changes in blood pressure. Specifically, terminal experiments at the appropriate ages will include metabolic studies, assessment of renal function (GFR and RPF), direct blood pressure in resting animals, plasma assays for catecholamines, corticosterone, PRA, AVP, and ANP, as well as catecholamine levels in discrete brainstem and hypothalamic nuclei, using the Palkovits micropunch technique. These data will answer questions related to the physiological and biochemical mechanisms of environmentally- induced hypertension, especially as they relate to """"""""family history.""""""""
Showing the most recent 10 out of 21 publications
