The overall objective of this proposal is to test the hypothesis that plasma HDL or one of its constituents contributes to regulation of PGI2 biosynthesis in the heart and vascular structures. To this effect the following specific objectives will be addressed. 1. Characterization of HDL effects on prostaglandin release in terms of tissue specificity and effect of specific lipoprotein constituents. We will extend investigation of the effects of HDL on prostaglandin release from the heart to other tissues including the rabbit kidney perfused with Tyrode solution, and slices of rabbit thoracin aorta and renal medulla incubated with Krebs solution. The effects of HDL constituents i.e., apoproteins, HDL subfractions lipid components, will be examined also. 2. Investigation of the mechanisms(s) underlying the effect of HDL in promoting prostaglandin release. We will define the effect of HDL and its active constituents on arachidonate release and on the activity of fatty acid cyclooxygenase, and prostaglandin endoperoxide metabolizing enzymes obtained from tissue structures that are found to release prostaglandins when challenged with HDL. 3. Evaluation of the relationship between HDL-induced promotion of prostaglandin release and vascular functions. We will study the effects of HDL and constituents on vascular tone and reactivity to vasoconstrictor hormones in the presence and absence of cyclooxygenase inhibitors so as to differentiate effects related to increased prostaglandin levels from those which are not. 4. Characterization of HDL effects on prostaglandin release in vivo. In the conscious rabbit we will compare the plasma levels of prostaglandins (PGE2, PGFAlpha, and 6-keto-PGF1Alpha) before and during intravenous infusion of HDL so as to produce graded elevations in plasma levels of the lipoprotein.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031403-03
Application #
3342493
Study Section
Biochemistry Study Section (BIO)
Project Start
1984-03-01
Project End
1988-02-29
Budget Start
1986-03-01
Budget End
1988-02-29
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163