Recent studies have demonstrated that altered central dopaminergic activity may play a role in the development of hypertension. The goal of the present research is to test the hypothesis that alterations in central dopaminergic neurons contribute to the pathogenesis of hypertension in the spontaneously hypertensive rat of the Okamoto strain (SHR) and the DOCA-NaCl hypertensive rat, two commonly used models of hypertension in which central and peripheral noradrenergic mechanisms have been shown to be altered. The first study will determine whether the central dopaminergic system has a role in modulating cardiovascular function in both normal and hypertensive animals. This will be accomplished by infusing specific dopamine (DA) agonists and antagonists intravenously or into the cerebral ventricular system or into specific cardiovascular regulatory regions of the hypothalamus and brainstem. The second study will characterize alterations in the release of DA from central dopaminergic neurons in SHR and DOCA-NaCl treated rats. Both in vivo push-pull and in vitro superfusion techniques will be employed to directly assess DA release from nuclei in these two animal models of hypertension. This will be accomplished by direct in vitro and in vivo analysis of DA release from brain regions rich in dopaminergic nerve terminals. This will provide the first direct demonstration of altered central DA function in an animal model of hypertension. Taken together, these studies will characterize the importance of the central dopaminergic system in cardiovascular control in normal and hypertensive individuals.
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