This project will investigate the several MACRO and MICROCIRCULATORY factors which act in concert to produce the elevated peripheral resistance seen in hypertension. It is our general hypothesis that there are MULTIPLE HEMODYNAMIC PATHWAYS to established hypertension, with the particular hemodynamic pattern individualized because of different cardiovascular reactivities. Our specific hypothesis is that different systemic and microvascular reactivities to environmental stressors and stimuli produce distinctive hemodynamic responses, which then cause more long-term vascular structural alterations. We also propose that these structural changes are brought about principally by factors involved in long-term autoregulation or local control of blood flow. Functional and structural alterations of the vasculature in hypertension have been extensively documented, in terms of internal diameter, wall thickness, total number of parallel arterioles and percentage of open vessels. Our approach to these hypotheses involves investigating systemic and microvascular reactivity in unanesthetized animals, determining the pathophysiological interaction of simultaneously applied vasoactive agents, research the local and neural factors controlling vascularity, and correlating these studies with findings in human essential hypertensives. The experimental models will be skeletal muscle and brain vasculature of the Dahl salt-sensitive rat (Dr. John Rapp strain), the Spontaneously Hypertensive Rat (SHR), and the chick chorioallantoic membrane (CAM).
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