Metabolic changes during antihypertensive therapies.

There is controversy whether various classes of antihypertensive drugs can reduce significantly cardiovascular morbidity and mortality in primary prevention. A failure to show this in many studies was attributed, at least in part, to deleterious effects of these drugs on lipid metabolism. Especially adrenergic antihypertensives cause marked effects on lipoprotein levels in plasma. A review of the literature revealed that beta-blockers increase triglycerides and VLDL (very low density lipoprotein)-cholesterol and may lower plasma HDL (high density lipoprotein) levels. In contrast alpha 1-adrenergic inhibitors like prazosin, doxazosin and terazosin lower triglycerides, total cholesterol, LDL (low density lipoprotein)- and VLDL-cholesterol and increase plasma HDL levels. The mechanisms by which alpha- and beta-blockers may produce the observed effects on plasma lipids and lipoproteins are not well understood. It has been shown in our laboratory that the activity of the LDL receptor of peripheral cells, a major determinant of cholesterol levels in plasma, is regulated by catecholamines via alpha 2- and beta 2-adrenergic receptors. Accordingly, blockade of these adrenoceptors with alpha- and beta-adrenergic antagonists can reverse the catecholamine effect. In addition these agents may affect lipoprotein lipase, lecithin cholesteryl acyltransferase and cholesterol ester hydrolase. These data may explain, at least in part, the plasma effects. However, long-term studies are needed to clarify the clinical value of antihypertensives with different metabolic profiles.