Woodside W F, Swindell A C
Department of Pharmacology, University of New Mexico Medical School, Albuquerque 87131.
J Cardiovasc Pharmacol. 1987;10 Suppl 9:S27-34.
Prazosin or doxazosin, selective alpha 1-adrenergic receptor inhibitors used in the treatment of hypertension, are known from clinical studies to lower plasma lipids. When diets and dosing regimens are carefully controlled, both agents produce similar effects on plasma lipids in rats, i.e., decreases in triglycerides and in the non-high density lipoprotein (non-HDL) fraction of cholesterol. In order to conduct these studies, models of rats partially fasting (PF) and eating a high-sucrose diet were developed. The effects of prazosin 2.3 mg/kg/day and doxazosin 20 mg/kg/day on plasma levels of triglycerides, total and HDL cholesterol, free fatty acids (FFA), ketones, and other metabolites were measured in rats in the fed, fasting, or PF states, at various times after a meal, and with a high-cholesterol diet. The pattern of responses leads to the hypothesis that, under conditions of partial or complete fasting, alpha 1-adrenergic receptor inhibition can alter intrahepatic FFA metabolism, causing increased ketogenesis and diminished triglyceride synthesis, possibly through potentiation of beta-adrenergic or related pathways. If these concepts prove to be valid in humans, they suggest that factors such as the rate of very-low-density lipoprotein (VLDL) production or the state of sympathetic nervous activity may influence the changes in lipids induced by these agents.
哌唑嗪或多沙唑嗪是用于治疗高血压的选择性α1肾上腺素能受体抑制剂，临床研究表明它们可降低血浆脂质水平。当饮食和给药方案得到严格控制时，这两种药物对大鼠血浆脂质产生相似的作用，即甘油三酯和胆固醇的非高密度脂蛋白（non-HDL）部分降低。为了进行这些研究，建立了部分禁食（PF）和高蔗糖饮食的大鼠模型。在喂食、禁食或PF状态下、餐后不同时间以及高胆固醇饮食条件下，测量了2.3mg/kg/天的哌唑嗪和20mg/kg/天的多沙唑嗪对大鼠血浆甘油三酯、总胆固醇和高密度脂蛋白胆固醇、游离脂肪酸（FFA）、酮及其他代谢物水平的影响。这种反应模式引出了一个假设，即在部分或完全禁食的情况下，α1肾上腺素能受体抑制可能会改变肝内FFA代谢，导致生酮增加和甘油三酯合成减少，这可能是通过增强β肾上腺素能或相关途径实现的。如果这些概念在人类中被证明是有效的，它们表明极低密度脂蛋白（VLDL）产生速率或交感神经活动状态等因素可能会影响这些药物引起的确脂质变化。
