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哇巴因样因子和钠钾泵在大鼠及人类遗传性高血压中的作用

Role of the ouabain-like factor and Na-K pump in rat and human genetic hypertension.

作者信息

Ferrandi M, Manunta P, Rivera R, Bianchi G, Ferrari P

机构信息

PRASSIS-Sigma Tau Research Institute, Settimo Milanese, Milan, Italy.

出版信息

Clin Exp Hypertens. 1998 Jul-Aug;20(5-6):629-39. doi: 10.3109/10641969809053241.

DOI:10.3109/10641969809053241
PMID:9682919
Abstract

Endogenous ouabain-like factor (OLF) is present in mammal tissues and after standardized extraction procedure can be similarly quantified by two independent assays: RIA and Na-KATPase inhibition. OLF was quantified both from plasma and tissues obtained from MHS hypertensive and MNS normotensive rats, maintained under the same environmental and dietary conditions, and from plasma of healthy volunteers and essential hypertensive patients. OLF biochemical characterization shows that it behaves like ouabain except for a 1000-fold higher affinity for the ouabain low-affinity Na-KATPase isoforms than ouabain. Tissue and plasma levels of OLF are higher in MHS than in MNS rats and are not influenced by exogenous OLF sources. Plasma OLF is also increased in a subgroup of hypertensive patients. Both in rats and humans a primary cell membrane alteration affecting ion transports seems to be linked to the increased levels of OLF. An antihypertensive compound which selectively antagonizes the pressor effect of OLF and corrects the ion transport defect is under development and can represent a new pharmacological approach to the treatment of hypertension.

摘要

内源性哇巴因样因子(OLF)存在于哺乳动物组织中,经过标准化提取程序后,可通过两种独立的测定方法进行类似的定量:放射免疫分析(RIA)和钠钾ATP酶抑制法。从处于相同环境和饮食条件下的MHS高血压大鼠和MNS正常血压大鼠获取的血浆和组织中,以及从健康志愿者和原发性高血压患者的血浆中,均对OLF进行了定量。OLF的生化特性表明,除了对哇巴因低亲和力钠钾ATP酶同工型的亲和力比哇巴因高1000倍外,它的行为与哇巴因相似。MHS大鼠的组织和血浆中OLF水平高于MNS大鼠,且不受外源性OLF来源的影响。高血压患者亚组的血浆OLF也有所升高。在大鼠和人类中,影响离子转运的原发性细胞膜改变似乎都与OLF水平升高有关。一种选择性拮抗OLF升压作用并纠正离子转运缺陷的抗高血压化合物正在研发中,它可能代表一种治疗高血压的新药理学方法。

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