To study the mechanisms by which
adrenergic antagonists affect blood pressure and plasma
lipid levels, the effects of alpha-blockade with
prazosin were compared with those of beta-blockade with
propranolol in 23 normolipidemic, mildly hypertensive patients. Plasma
lipoprotein composition,
apolipoproteins, and some of the processes involved in
lipid synthesis and clearance from plasma were investigated also. Patients entered an eight-week placebo period during which they were free of all
antihypertensive medications. They were then randomly assigned under double-blind conditions to treatment with either
prazosin (mean dose, 5 mg per day) or
propranolol (mean dose, 133 mg per day) for eight weeks. Doses of both drugs were titrated to achieve either a decrease in diastolic blood pressure of 10 mm Hg or more or a reduction of diastolic blood pressure to less than 85 mm Hg, whichever was lower. Total plasma
cholesterol decreased by 9 percent during
prazosin treatment and increased by 7 percent during
propranolol treatment (p less than 0.005 between treatments).
Low-density lipoprotein cholesterol decreased by 12 percent with
prazosin and increased by 12 percent with
propranolol (p less than 0.005).
Apolipoprotein B decreased by 17 percent with
prazosin and increased by 15 percent with
propranolol (p less than 0.005). There were no significant changes in total
high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 or high-density lipoprotein3, or in
apolipoprotein A1 and
apolipoprotein A2. Plasma
very low-density lipoprotein and
low-density lipoprotein triglycerides were not significantly affected by either treatment. Plasma
post-heparin lipase activities, which clear
triglyceride and
high-density lipoprotein cholesterol from plasma, were not altered significantly. Since regional blood flow could affect the clearance of plasma
lipoproteins, measurements were taken of forearm blood flow, forearm vascular resistance, and maximal forearm vasodilatory potential during
reactive hyperemia. The
adrenergic antagonists had no effect on these measurements, nor did they affect cellular
cholesterol synthesis as measured by the activity of 3-hydroxy-3-methylglutaryl
coenzyme A reductase in blood mononuclear cells. The results of this study demonstrate differing actions between alpha- and beta-
adrenergic antagonism. Alpha-blockade produced significantly lower levels of plasma
low-density lipoprotein cholesterol and
apolipoprotein B than beta-
adrenergic antagonism without changes in
high-density lipoproteins.