Sacks F M, Creager M A, Gallagher S J, Loscalzo J, Dzau V J
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Med. 1989 Jan 23;86(1B):8-13. doi: 10.1016/0002-9343(89)90121-6.
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.
为研究肾上腺素能拮抗剂影响血压和血浆脂质水平的机制，在23例血脂正常、轻度高血压患者中，比较了哌唑嗪α受体阻滞与普萘洛尔β受体阻滞的效果。还研究了血浆脂蛋白组成、载脂蛋白以及血浆脂质合成与清除过程中的一些环节。患者进入为期8周的安慰剂期，在此期间停用所有抗高血压药物。然后在双盲条件下将他们随机分为两组，分别接受哌唑嗪（平均剂量为每日5毫克）或普萘洛尔（平均剂量为每日133毫克）治疗8周。两种药物的剂量均进行滴定，以使舒张压降低10毫米汞柱或更多，或使舒张压降至85毫米汞柱以下，以较低者为准。在哌唑嗪治疗期间，血浆总胆固醇下降了9%，而在普萘洛尔治疗期间升高了7%（两种治疗之间p<0.005）。低密度脂蛋白胆固醇在哌唑嗪治疗时下降了12%，在普萘洛尔治疗时升高了12%（p<0.005）。载脂蛋白B在哌唑嗪治疗时下降了17%，在普萘洛尔治疗时升高了15%（p<0.005）。总高密度脂蛋白胆固醇、其亚组分高密度脂蛋白2或高密度脂蛋白3，以及载脂蛋白A1和载脂蛋白A2均无显著变化。两种治疗对血浆极低密度脂蛋白和低密度脂蛋白甘油三酯均无显著影响。从血浆中清除甘油三酯和高密度脂蛋白胆固醇的血浆肝素后脂肪酶活性也无显著改变。由于局部血流可能影响血浆脂蛋白的清除，因此在反应性充血期间测量了前臂血流量、前臂血管阻力和最大前臂血管舒张潜能。肾上腺素能拮抗剂对这些测量值无影响，对通过血液单核细胞中3-羟基-3-甲基戊二酰辅酶A还原酶活性测定的细胞胆固醇合成也无影响。本研究结果表明α和β肾上腺素能拮抗作用存在不同效应。与β肾上腺素能拮抗作用相比，α受体阻滞导致血浆低密度脂蛋白胆固醇和载脂蛋白B水平显著降低，而高密度脂蛋白无变化。
