Effects of Antihypertensive Agents Propranolol, Metoprolol, Nadolol, Prazosin, and Chlorthalidone on ACAT Activity in Rabbit and Rat Aortas and on LCAT Activity in Human Plasma In Vitro

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Abstract
Summary: Various antihypertensive agents were studied in vitro to determine their effects on cholesterol esterification by arterial ACAT (acylCoA:cholesterol acyltransferase; E.C. 2.3.1.26) and on the activity of plasma LCAT (lecithin:cholesterol acyltransferase; E.C. 2.3.1.43). Propranolol inhibited ACAT in normal rat aorta, atheromatous rabbit aorta, and in isolated microsomes from atheromatous rabbit aorta. Inhibition reached 50% in microsomes at ×0.8 mM. Metoprolol, prazosin, and chlorthalidone also inhibited microsomal ACAT, but to a lesser extent than propranolol; nadolol had no effect on the enzyme. Propranolol, metoprolol, prazosin, and chlorthalidone also inhibited LCAT in human plasma, whereas nadolol showed no inhibitory effect. Fifty percent inhibition occurred at 2 mM with prazosin and chlorthalidone and at 4–5 mM with propranolol. Metoprolol showed a weak dose-dependent inhibition that ranged from 2 to 10% over the concentration range 0.5–5 mM. The data suggest a mechanistic basis for altered lipoprotein profiles observed clinically with certain antihypertensive therapies and suggest that a direct effect of β- blockers on arterial wall metabolism may account for their recognized ability to reduce the development of experimental atherosclerosis and to improve survival in post–myocardial infarction patients.