The overall goal of the PPG is to elucidate cellular/molecular mechanisms of blood pressure regulation important for determining vascular tone and sodium homeostasis. Projects are directed at gaining a better understanding of angiotensin and vasopressin receptors, cellular signaling pathways and transporters that are regulated, how different components interact, mechanisms responsible for Ca metabolism in vascular smooth muscle and ascertaining the link between cytochrome P450 dependent arachidonic acid signaling, Na and Ca homeostasis and human hypertension. This goal necessitates a multidisciplinary group encompassing disciplines of cell organ physiology, molecular biology, biochemistry, biophysics which we have assembled. The program stresses a broad application to the problem of receptors, effectors and coupling mechanisms employing humans, animals, cells and subcellular organnels and emphasizes the application of state-of-the-art techniques. Studies at a cellular level will employ fluorescent probes to assess receptor mediated signal transduction, ion transport, steady-state intracellular ions, electron probe microanalysis, and patchclamping. Studies at a molecular level involve cloning receptor subtypes, transfections of receptors and enzymes for determination of the regulatory roles of GTP binding proteins, phospholipases and P450 isozymes in signal transduction of smooth muscle cells and transporting epithelium. Studies in human are aimed at determining the critical role of cytochrome P450 system in salt sensitive hypertension. Cores provide administrative, tissue culture, animal models and state-of-the art instrumentation to enhance scientific merit of all projects.
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