Cress L W, Freas W, Haddy F, Muldoon S M
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Hypertension. 1991 Oct;18(4):516-22. doi: 10.1161/01.hyp.18.4.516.
Abundant experimental data suggest that an endogenous digitalislike factor is responsible for some essential hypertension. Some forms of hypertension have also been associated with increased levels of catecholamines. We therefore designed experiments to investigate the role of digitalislike factors in the regulation of norepinephrine turnover in the neurovascular junction. We chose bufalin, an amphibian-derived compound that shares many of the physiological properties postulated as characteristic of digitalislike compounds, as a model of the mammalian compound. In vitro experiments in canine saphenous veins showed that, in addition to inhibiting norepinephrine uptake, bufalin increased norepinephrine overflow by an amount larger than could be explained solely by uptake inhibition. The effect of bufalin on norepinephrine overflow is inhibited by tetrodotoxin, which suggests a dependence of this response on Na+ influx through the neuronal membranes. We propose that Na+,K(+)-ATPase inhibition resulting in neuronal depolarization is responsible for the augmented norepinephrine turnover caused by bufalin and that these indirect effects of norepinephrine on the cardiovascular system may play a role in the etiology of hypertension.
大量实验数据表明，一种内源性类洋地黄因子与某些原发性高血压有关。某些形式的高血压也与儿茶酚胺水平升高有关。因此，我们设计了实验来研究类洋地黄因子在神经血管连接处去甲肾上腺素周转调节中的作用。我们选择蟾毒灵，一种源自两栖动物的化合物，它具有许多被假定为类洋地黄化合物特征的生理特性，作为哺乳动物化合物的模型。在犬隐静脉的体外实验表明，除了抑制去甲肾上腺素摄取外，蟾毒灵使去甲肾上腺素溢出量增加，其增加幅度大于仅由摄取抑制所能解释的量。蟾毒灵对去甲肾上腺素溢出的作用被河豚毒素抑制，这表明该反应依赖于通过神经元膜的Na+内流。我们提出，Na+,K(+)-ATP酶抑制导致神经元去极化是蟾毒灵引起去甲肾上腺素周转增加的原因，而去甲肾上腺素对心血管系统的这些间接作用可能在高血压的病因学中起作用。
