title: Effects of alpha- and beta-adrenergic antagonists on plasma apolipoproteins and forearm blood flow in patients with mild hypertension.
abstract: 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.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: F M
authors.initials: FM
authors.lastname: Sacks
authors.forename: M A
authors.initials: MA
authors.lastname: Creager
authors.forename: S J
authors.initials: SJ
authors.lastname: Gallagher
authors.forename: J
authors.initials: J
authors.lastname: Loscalzo
authors.forename: V J
authors.initials: VJ
authors.lastname: Dzau
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D008049:Lipase / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000627:therapeutic use*; D011433:Propranolol / Q000627:therapeutic use*; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D001053:Apolipoproteins; D008055:Lipids; D011433:Propranolol; D006904:Hydroxymethylglutaryl-CoA Synthase; D008049:Lipase; D011224:Prazosin