Effects of adrenergic antihypertensive drugs on sterol synthesis in freshly isolated human mononuclear leukocytes.
The effects of the adrenergic antihypertensive drugs propranolol, clonidine, alpha-methyldopa, urapidil, indoramin, and prazosin on the relative rate of sterol synthesis were studied in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a threefold increase in the incorporation of [14C]acetate or tritiated water into sterols. (-)-Epinephrine added at zero time to the incubation medium inhibited the relative rate of sterol synthesis by 32% at a concentration of 1 mumol/L. The non-specific beta-blocker propranolol, added at equimolar concentrations, almost abolished the epinephrine-induced suppression. The beta-blocker per se had no effect on the incorporation of [14C]acetate into sterols up to a concentration of 1 mumol/l. The alpha 2-agonist clonidine and alpha-methyldopa, added in increasing concentrations at zero time, inhibited the relative rate of sterol synthesis, yielding a sigmoidal log dose-effect curve. The suppression was 43 and 24%, respectively, at a concentration of 0.1 mmol/L. The alpha 1-antagonists indoramin, prazosin, and urapidil, up to a concentration of 10 mumol/L, had no effect per se, or on the epinephrine-induced suppression of the relative synthesis rate of sterols. The results give evidence that various antihypertensive adrenergic drugs, depending on their action on beta- or alpha-adrenergic receptors, have different effects on cholesterol biosynthesis and therefore may affect cellular cholesterol homeostasis.
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Krone
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Müller-Wieland
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Greten
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis*; D013566:Sympathomimetics / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D008055:Lipids; D013261:Sterols; D013566:Sympathomimetics; D004837:Epinephrine