The proposed research program focuses on diacylglycerol formation in vascular smooth muscle. Diacylglycerol (DG), one of the major putative second messengers of the phosphoinositide system, will be measured in both cultured vascular smooth muscle cells (VSMC) and intact rat aorta. Biochemical and physiological mechanisms controlling agonist-induced DG formation will be defined, and the role of DG in sustaining vascular smooth muscle contraction will be examined. Radioisotopic labelling, subcellular fractionation, and chromatogtaphic separation will be used to quantitate and localize lipids, and measurement of isometric force developed by ring segments of aorta will be used to quantitate contraction.
Specific aims i nclude: 1) determining the ionic and endocytotic mechanisms controlling sustained angiotensin II-induced DG formation in VSMC; 2) characterizing angiotensin II- and norepinephrine-stimulated phosphoinositide hydrolysis and DG production in intact rat aorta and comparing it with that produced by angiotensin II in VSMC; 3) determining the physiological or biochemical bases for any observed differences in phosphoinositide metabolism between cultured cells and intact aorta; and 4) determining whether DG/protein kinase C has a role in sustaining vascular smooth muscle contraction. These studies should provide important basic information on the cellular mechanisms controlling the sustained phosphoinositide response in vascular smooth muscle and their relationship to contraction. Understanding the mechanisms of normal vascular responsiveness should provide insight into the pathophysiology of hypertension and atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038206-04
Application #
3470992
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1988-07-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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