The research proposal concerns investigation of factors or naturally occurring agents which control and modulate the release of arachidonic acid (AA) and the major metabolic pathway of AA to prostacyclin (PGI2) or thromboxane (TxA2) in the intact and damaged blood vessels. Further investigation of the release and the ultimate fate of PGI2 in the circulation will then be related to the possible physiological mechanism in the regulation of blood pressure, control of vascular reactivity and platelet aggregation. Tissue slices and subcellular fractions of bovine mesenteric blood vessels or normal and hypertensive rat aortas will be used for studies of the enzymes (phospholipase A2, cyclo-oxygenase, prostacyclin synthetase and thromboxane synthetase) which are intimately involved in the biosynthesis of PGI2. Factors or agents (e.g., angiotensins I and II, bradykinin) which may modulate the transformation of endoperoxides (PGG2 or H2) to PGI2 or TxA2 will be investigated. The metabolism of PGI2 and TxB2 will be studied both in vitro as well as in isolated perfused mesenteric blood vessels from normal and hypertensive rats using 3H-labeled PGI2 or TxB2 as substrate. The metabolites of PGI2 and TxB2 in blood vessels will be isolated and examined by GC-MS. Factors or agents which modulate the major metabolic enzymes (15-OH-prostaglandin dehydrogenase; 9-OH-prostaglandin dehydrogenase and PGE-9-ketoreductase) will also be investigated. These proposals are designed to study the control and regulation of PGI2 and thromboxane biosynthesis, their release and metabolic fate. Results of these studies will be used to relate disorders of biosynthesis and metabolism of PGI2, TxA2 and other prostaglandins in normal and damaged blood vessels and their relationship to hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL025316-07
Application #
3338029
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1979-09-30
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
New York Medical College
Department
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
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