Prostaglandin and HETE synthesis by aortae and hearts of normal and atherosclerotic rabbits.

New Zealand white rabbits were fed a diet enriched with cholesterol (0.25%) for 4 months. At that time, the aortae and coronary vessels of the cholesterol-fed rabbits were extensively covered with atherosclerotic lesions while those of age-matched control rabbits were normal. Langendorff-perfused hearts from the rabbits were compared for their ability to release PGI2 and PGE2 into the coronary sinus effluent during basal perfusion and after exposure to a bolus injection of 50 mumoles of arachidonic acid. No differences were detected in prostaglandin production between the cholesterol-fed and control animals. Nor were any differences in coronary hemodynamics observed. Aortic arachidonic acid metabolism was studied in an intimal en-face preparation. No differences were observed in the basal release of the PGI2 metabolite, 6-keto-PGF1 alpha, or PGE2. PGI2 and PGE2 production increased in response to arachidonic acid and to the calcium ionophore, A23187, but no differences were observed between cholesterol-fed or control tissues. Using minced aortic tissue, the production of 5-, 11-, 12- and 15-hydroxyeicosatetraenoic acids (HETE) were quantified by GC/MS. Differences in basal or A23187-stimulated HETE biosynthesis were not detected between the normal and atherosclerotic rabbit tissues. The data demonstrate that alterations in vascular prostaglandin and HETE are not prominent in rabbits with stable atherosclerosis produced by 4 months of cholesterol feeding.