Effects of Various Antihypertensive Agents on Lipid Metabolism: Alterations in the Pattern of Lipids Synthesized from [14C]Oleate in Rat Liver In Vitro

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Abstract
Summary: The effects of five antihypertensive agents on lipid biosynthesis from [1-14C]oleate were studied in rat liver minces. At a level of 1 mM, propranolol and prazosin increased the incorporation of [14C)]oleate into diglycerides and cholesteryl esters by two- to fourfold and increased total phospholipid labeling by 20–30%. Chlorthalidone and metoprolol at 1 mM also stimulated the incorporation of [14C]oleate into phospholipids and diglycerides (20–50%) but did not affect its incorporation into triglycerides or cholesteryl esters. All four of the compounds statistically significantly inhibited the incorporation of [14C]oleate into phosphatidylcholine by 12–37% but stimulated incorporation into phosphatidylinositol by 17–95%. Nadolol differed from the other compounds in that it did not show selective effects but rather inhibited the incorporation of [14C]oleate into all lipid classes by ×50%. The data are discussed in terms of possible mechanisms involved in the lipid synthesis patterns and suggest the possibility that plasma lipid/lipoprotein changes observed in patients undergoing antihypertensive therapy may reflect, in part, altered hepatic lipid synthesis.