SODIUM-INDUCED HYPERTENSION AND THE ENDOGENOUS DIGITALISLIKE FACTOR OF THE HYPOTHALAMIC ORIGIN

哇巴因的灵敏ELISA已被开发用于测量非常低水平的内源性哇巴因样因子（OLF）。通过使用催化的报告物沉积来放大光密度，灵敏度水平为pg/孔级。当用这种ELISA系统分析尿样时，DOCA-盐高血压大鼠的尿OLF排泄量明显高于对照大鼠。还检查了OLF的组织分布;其在垂体、肾上腺和下丘脑中的含量较高，顺序为降序。哇巴因单克隆抗体免疫组化研究表明，OLF阳性神经元仅分布于下丘脑室旁核和视上核，其纤维分布于第三脑室室周器周围，肾上腺髓质也有OLF阳性神经元。为了探讨中枢单胺能神经元参与下丘脑OLF释放的可能性，侧脑室注射6-羟基多巴胺（OHDA）。6-OHDA显著降低了OLF的血浆水平，同时伴随着垂体和下丘脑中OLF含量的类似降低，但肾上腺中的OLF含量没有降低。因此，提示血浆OLF来源于下丘脑，而非肾上腺。OLF在高血压病中的作用也进行了研究，规律的轻度运动可显著降低血压，同时血浆OLF水平也显著降低，提示OLF在高血压病中也发挥着重要的血压调节作用。

The sensitive ELISA for ouabain has been developed to measure the very low level of endogenous ouabainlike factors (OLF). The level of the sensitivity was pg/well order by the use of catalyzed reporter deposition to amplify the optical density. When the urine sample was assayd by this ELISA system, urinary excretion of OLF was markedly elevated in DOCA-salt hypertensive rats as compared to the control rats. The tissue distribution of the OLF was also examined ; it was high in the pituitary, the adrenal and the hypothalamus in this decreasing order. In support of this, immunohistochemical study by the monoclonal antibody for ouabain revealed that the neuron containing OLF was restricted in the hypothalamic paraventricular nuclei and the supraoptic nuclei and the fibers distributed around the circumventricular organs of the third ventricle, and that the immunoreactivity existed in the adrenal medulla too. To explore the possible involvement of the central monoaminergic neurons in the release of OLF from the hypothalamus, 6-hydroxydopamine (OHDA) was given intracerebroventricularly. Six-OHDA significantly reduced the plasma level of OLF,which was accompanied by the similar reduction of OLF content in the pituitary and the hypothalamus but not in the adrenal. Therefore, it was suggested that the plasma OLF was of the hypothalamic origin, but not of the adrenal. The implication of OLF in the human hypertension was also investigated ; regular mild exercise decreased blood pressure significantly, which was accompanied by the significant reduction in plasma levels of OLF.These findings indicate that OLF has been playing significant roles in blood pressure regulation even in human essential hypertension.