The primary goal of this program project is to determine the properties of vascular smooth muscle (VSM) that regulate its contractile state, and hence blood flow, under physiological conditions and subsequently in hypertension. Since numerous factors may play a role in altering VSM contractility, and since so little is known about this important tissue a multifaceted study will be undertaken involving 13 faculty members who represent the Departments of Biochemistry, Pharmacology and Physiology. The 8 projects deal with the metabolism of VSM ("Energy metabolism and protein turnover in VSM") "VSM response to serum lipoproteins", "Vasoactive metabolites from VSM and parenchymal tissue", "Cyclic nucleotide metabolism in smooth muscle cultures" and "Effects of cyclic nucleotide stimulated phosphorylation on contractile system"), the mechanics of VSM ("The contractile system of VSM"), the pharmacology of VSM ("Norepinephrine release in and reactivity of VSM") and "The electrophysiology of VSM". The various projects are closely related so that there will be considerable interaction among the participants. A summary of the individual projects is given at the beginning of each proposal. The experiments include whole animal studies, isolated tissues and organs, VSM cell cultures and subcellular fractions, and core facilities are provided to meet the experimental needs of the investigators. An electron microscope facility is already present in the Physiology Department and a VSM cell culture facility has just been started. A third core facility for a steady supply of spontaneously hypertensive rats and suitable controls is planned for the second year of the program project. The information to be gained from this program project will not only provide necessary basic data on the mechanisms involved in the function of VSM but may well lead to more rational approaches for the treatment of disease caused by abnormally functioning VSM.