Nanjee M N, Miller N E
Department of Chemical Pathology and Metabolic Disorders, St. Thomas' Campus, United Medical School of Guy's Hospital, London, U.K.
J Cardiovasc Pharmacol. 1987;10 Suppl 9:S35-41.
Tissue culture studies have provided evidence that alpha 1-adrenergic receptor inhibition with doxazosin increases the number of low-density lipoprotein (LDL) receptors in human fibroblasts. A similar effect occurring in vivo might explain the reduction of plasma LDL concentration observed in some clinical trials of prazosin. In order to examine this question further, mice were given doxazosin 100 or 400 micrograms/kg/day by i.p. injection for 4 days, after which they were killed, blood was collected and livers were excised. Binding of 125I-labelled human LDL to tissue homogenates, over the concentration range 30-120 micrograms LDL protein/ml, was measured at 37 degrees C in the absence and presence of excess unlabelled LDL. Woolf plots of the results for saturable binding were found to be compatible with a single class of binding site. In control animals Bmax for this receptor was 867 +/- 117 ng LDL protein/mg tissue protein, and the equilibrium dissociation constant was 32.7 +/- 6.6 micrograms LDL protein/ml (mean +/- SD, n = 5). Doxazosin treatment had no effect on either parameter of 125I-LDL binding. A trend towards a decrease in liver triglyceride concentration with increasing doses of doxazosin was recorded, but there was no evidence for effects on liver cholesterol or serum lipid concentrations.
组织培养研究已提供证据表明，用多沙唑嗪抑制α1 - 肾上腺素能受体会增加人成纤维细胞中低密度脂蛋白（LDL）受体的数量。在体内发生的类似效应可能解释了在哌唑嗪的一些临床试验中观察到的血浆LDL浓度降低。为了进一步研究这个问题，通过腹腔注射给小鼠给予100或400微克/千克/天的多沙唑嗪，持续4天，之后将它们处死，采集血液并切除肝脏。在不存在和存在过量未标记LDL的情况下，于37℃测量30 - 120微克LDL蛋白/毫升浓度范围内125I标记的人LDL与组织匀浆的结合。发现饱和结合结果的伍尔夫图与单一类别的结合位点相符。在对照动物中，该受体的Bmax为867±117纳克LDL蛋白/毫克组织蛋白，平衡解离常数为32.7±6.6微克LDL蛋白/毫升（平均值±标准差，n = 5）。多沙唑嗪治疗对125I - LDL结合的任何参数均无影响。记录到随着多沙唑嗪剂量增加，肝脏甘油三酯浓度有下降趋势，但没有证据表明对肝脏胆固醇或血清脂质浓度有影响。
