Yuan W, Wang H, Lü Z
Department of Cardiology, The First Teaching Hospital, Xi'an Medical University, Xi'an 710061, China.
Zhonghua Nei Ke Za Zhi. 2001 Feb;40(2):105-8.
To compare the effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump alpha-subunit expression in myocardium of rats.
Normal Sprague-Dawley (SD) rats were injected with ouabain, digoxin or normal saline (NS) everyday and indirect SBP was recorded once a week. Six weeks later, all the rats were killed and sodium pump alpha1-, alpha2-, and alpha3-subunit were detected in the left ventricular myocardium with RT-PCR method and immunohistochemical assay at mRNA and protein levels.
At the end of six weeks SBP of rats infused with ouabain increased significantly (132.6 +/- 9.0 vs 115.7 +/- 8.2 mm Hg, P < 0.01), while no difference of SBP was found between digoxin group and NS group. The effects of ouabain and digoxin on sodium pump alpha-subunit isoform expression in myocardium were also different: both ouabain and digoxin stimulated expression of alpha3-isoform whereas alpha2-isoform unchanged at both mRNA and protein levels. alpha1-isoform was decreased in ouabain group and alpha1-isoform unchanged in digoxin group at both mRNA and protein levels.
It is suggested that both ouabain and digoxin could regulate sodium pump alpha-subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and might be responsible for the difference between the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.
比较哇巴因和地高辛对大鼠收缩压(SBP)及心肌钠泵α亚基表达的影响。
将正常的Sprague-Dawley(SD)大鼠每日注射哇巴因、地高辛或生理盐水(NS),每周记录一次间接SBP。六周后,处死所有大鼠,采用RT-PCR法和免疫组化法在mRNA和蛋白质水平检测左心室心肌钠泵α1、α2和α3亚基。
六周结束时,注射哇巴因的大鼠SBP显著升高(132.6±9.0 vs 115.7±8.2 mmHg,P<0.01),而地高辛组和NS组之间SBP无差异。哇巴因和地高辛对心肌钠泵α亚基异构体表达的影响也不同:哇巴因和地高辛均刺激α3异构体的表达,而α2异构体在mRNA和蛋白质水平均无变化。哇巴因组α1异构体在mRNA和蛋白质水平均降低,地高辛组α1异构体在mRNA和蛋白质水平均无变化。
提示哇巴因和地高辛均可调节钠泵α亚基异构体表达,这可能与内源性哇巴因的生理作用有关,可能是哇巴因和地高辛药理和毒理作用差异的原因,包括它们对血压的影响。