High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: relationship to cardiac arachidonate mobilization.
The objectives of this study were to characterize the effects of plasma lipoproteins on prostacyclin (PGI2) production by the Langendorff-perfused rabbit heart, and to determine the mechanism of lipoprotein-induced cardiac PGI2 production. PGI2 production by perfused rabbit hearts was stimulated by injections of rabbit very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). HDL was much more effective than equivalent doses of VLDL or LDL. Infusion of HDL at a physiological concentration stimulated cardiac PGI2 output by 417%, but infusion of VLDL or LDL was ineffective. Cardiac PGI2 production increased from 47% to 340% with increasing doses of HDL. The release of cardiac PGI2 in response to injections or infusions of HDL occurred rapidly; maximal release of PGI2 was reached within 2 min after exposure to HDL. Injections of HDL stimulated the production of [3H]arachidonic acid, [3H]prostaglandin E2, [3H]prostaglandin F2 alpha, and [3H]6-keto-prostaglandin F1 alpha from hearts after prelabeling of cardiac lipids with [3H]arachidonic acid. These results indicate that plasma lipoproteins, specifically HDL, stimulate PGI2 production by the isolated rabbit heart. The mechanism by which HDL increases cardiac PGI2 production may involve the mobilization of cardiac arachidonic acid for PGI2 synthesis.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D011817:Rabbits
D001095:Arachidonic Acids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D010740:Phospholipases; D001920:Bradykinin