Effects of various antihypertensive agents on lipid metabolism: alterations in the pattern of lipids synthesized from [14C]oleate in rat liver in vitro.
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 approximately 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.
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002752:Chlorthalidone / Q000494:pharmacology; D002788:Cholesterol Esters / Q000096:biosynthesis; D004075:Diglycerides / Q000096:biosynthesis; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009248:Nadolol; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D014280:Triglycerides / Q000096:biosynthesis
D000959:Antihypertensive Agents; D002788:Cholesterol Esters; D004075:Diglycerides; D008055:Lipids; D009829:Oleic Acids; D010743:Phospholipids; D011412:Propanolamines; D014280:Triglycerides; D019301:Oleic Acid; D009248:Nadolol; D011433:Propranolol; D008790:Metoprolol; D002752:Chlorthalidone; D011224:Prazosin