Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
Braz J Med Biol Res. 2011 Sep;44(9):933-8. doi: 10.1590/s0100-879x2011007500103. Epub 2011 Aug 19.
Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na(+) pump, inhibiting its activity. Inhibition of this pump increases intracellular Na(+), which reduces the activity of the sarcolemmal Na(+)/Ca(2+) exchanger and thereby reduces Ca(2+) extrusion. Consequently, intracellular Ca(2+) increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.
哇巴因是一种内源性的洋地黄化合物，在几种哺乳动物的血浆中以纳摩尔浓度被检测到，与高血压的发生有关。此外，几种高血压模型中血浆哇巴因增加，哇巴因的急性或慢性给药会增加啮齿动物的血压。这些结果表明哇巴因与动脉高血压的发生、发展和维持之间可能存在关联。这种关联的一个解释是，哇巴因与 Na(+)泵的α亚基结合，抑制其活性。该泵的抑制作用会增加细胞内 Na(+)，从而降低肌膜 Na(+)/Ca(2+)交换器的活性，从而减少 Ca(2+)外排。因此，细胞内 Ca(2+)增加并被肌浆网摄取，肌浆网激活后会释放更多的钙并增加血管平滑肌张力。事实上，哇巴因的急性治疗会增强血管对加压剂的反应性，增加血管周围肾上腺素能神经末梢去甲肾上腺素的释放，并促进血管床内皮血管紧张素转换酶的活性和局部血管紧张素 II 的合成增加。此外，哇巴因引起的高血压与中枢机制有关，这些机制会增加交感神经张力，这是大脑肾素-血管紧张素系统激活后的结果。因此，外周机制和中枢机制（主要涉及肾素-血管紧张素系统）的关联可能有助于解释哇巴因引起的动脉血压升高的急性作用。
