This is a renewal application for a set of experiments intended to explore the hypothesis that increases in blood pressure over time depend on increased arterial smooth muscle mass in the walls of resistance vessels. We suggest that these increases in mass are due to """"""""remodeling,"""""""" a general mechanism for adaptation of blood vessels to increased physiological demands. We have found that increases in vascular mass are associated with smooth muscle DNA replication, raising the possibility that the increased DNA content may provide a form of memory leading to further increases in blood pressure via a positive feedback loop. In exploring this hypothesis we have recently learned that vasoactive agents are not themselves sufficient to elicit DNA synthesis in arterial smooth muscle in vivo despite having the ability to induce expression of genes required for DNA synthesis. The experiments in this proposal attempt to determine whether increased DNA content in hypertensive artery walls does predispose to further increases in vascular mass, to identify the additional condition(s) required for entry into DNA synthesis following a vasoactive stimulus, and to separate the roles of the three vessel wall cells, endothelial cells, smooth muscle cells and nerves in the remodeling of hypertensive vessel walls.
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