Complications from untreated essential hypertension (HT) represent the number one killer today in the United States. In an attempt to understand the mechanisms responsible for the development of HT in humans, many investigators have turned to research with animal models. Although a great deal has been learned, there have been few studies which address environmental variables and the role that various environmental factors such as diet, exercise, stress, etc., are believed to play in HT in humans. The relative paucity of such studies reflects the absence of an appropriate model, one which becomes hypertensive only following exposure to the appropriate environmental factors. Recently, a rat model has been developed which shows considerable promise for such studies. The present proposal seeks to begin to study the mechanisms responsible for this environmentally-induced HT. Specifically, the first study seeks to characterize the hemodynamic response of these animals as they develop HT produced by daily exposure to aversive conditioning. Blood flow probes around the ascending aorta and arterial canulae in the abdominal aorta will be implanted in order to determine the hemodynamic characteristics of this HT as it develops, such as the relationship between cardiac output and peripheral resistance, and the relationship between acute and chronic blood pressure changes. Another mechanism which is suspected of playing a role in HT concerns resetting of the baroreceptors. Baroreceptor function will be assessed by studies involving phenylephrine infusions, sinoaortic denervation, and light microscopic study of carotid arteries. Another set of studies will begin to evaluate the role that the CNS plays in this model of HT. Both adrenergic and cholinergic systems will be studied, especially in the brainstem and forebrain. Further studies will seek to determine what role the kidney plays in this model, especially those apsects of renal function which are influenced by the CNS. Since a chronic exercise program has been demonstrated to attenuate stress-induced HT in this model, studies will seek to characterize the central and peripheral correlates of this phenomenon. Finally, in the last year of this proposal, the P.I. seeks to spend 9-12 months in the laboratory of a prominent researcher in the area of CNS mechanisms in HT, in order to gain additional insight into how potential mechanisms tie together. Following the RCDA, future studies will focus on further clarifying those mechanisms most clearly linked to HT in the animal model.
