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.
| Van Sickle, W A; Wilcox, H G; Nasjletti, A (1986) HDL-induced cardiac prostacyclin synthesis: relative contribution of HDL apoprotein and lipid. Biochem Biophys Res Commun 139:416-23 |
| Van Sickle, W A; Wilcox, H G; Malik, K U et al. (1986) High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: relationship to cardiac arachidonate mobilization. J Lipid Res 27:517-22 |
| Erman, A; Baer, P G; Nasjletti, A (1985) Augmentation of unesterified arachidonic acid in the renal inner medulla of dexamethasone-treated rats. Relationship to altered triglyceride metabolism. J Biol Chem 260:4679-83 |
