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一氧化氮供体奥沙康对实验动物不同给药途径的降压作用。

The hypotensive effect of the nitric monoxide donor Oxacom at different routs of its administration to experimental animals.

作者信息

Тimoshin Alexander А, Lakomkin Vladimir L, Аbramov Alexander А, Ruuge Enno K, Kapel'ko Valery I, Chazov Evgeny I, Vanin Anatoly F

机构信息

Russian Cardiology Research-and-Production Complex, Russian Ministry of Health, Moscow, Russia.

N.N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.

出版信息

Eur J Pharmacol. 2015 Oct 15;765:525-32. doi: 10.1016/j.ejphar.2015.09.011. Epub 2015 Sep 12.

Abstract

Earlier it has been found that the hypotensive drug Oxacom containing binuclear dinitrosyl iron complexes (B-DNIC) with glutathione can effectively decrease, as a nitric monooxide (NO) donor, the mean arterial pressure (МАР) in rats upon intravenous bolus injection in the form of an aqueous solution (Chazov et al., 2012). The aim of this study was to investigate the hypotensive effects of Oxacom administered to experimental rats by intravenous, intramuscular, subcutaneous, intraperitoneal, intragastric, rectal routes.MAP and heart rate (HR) were measured with the help of arterial catheters equipped with tensometric sensors. Oxacom was administered to rats at the dose of 2.0 μmole of B-DNIC/kg. The concentration of paramagnetic mononuclear protein-bound DNIC (М-DNIC) formed in the blood and tissues of various internal organs of the rat was determined by the EPR method. Upon subcutaneous, intramuscular or intraperitoneal administration of Oxacom, the maximum amplitude of the МАР decrease varies from 30% to 70%, respectively, in comparison with the corresponding parameter for the intravenously injected Oxacom. Another difference is the lack of the fast phase in the initial stage of the МАР decrease and the longer persistence of protein-bound M-DNIC formed in the circulating blood after intramuscular, subcutaneous or intraperitoneal administration of Oxacom. Thus, the NO donor Oxacom exerts pronounced hypotensive effects on rats not only upon intravenous, but also upon intramuscular, subcutaneous or intraperitoneal administration.

摘要

此前已发现,含有与谷胱甘肽形成的双核二亚硝酰基铁配合物(B-DNIC)的降压药奥沙康,作为一氧化氮(NO)供体,在以水溶液形式静脉推注时能有效降低大鼠的平均动脉压(МАР)(查佐夫等人,2012年)。本研究的目的是研究通过静脉、肌肉、皮下、腹腔、胃内、直肠途径给实验大鼠施用奥沙康的降压效果。借助配备张力传感器的动脉导管测量МАР和心率(HR)。以2.0微摩尔B-DNIC/千克的剂量给大鼠施用奥沙康。通过电子顺磁共振(EPR)方法测定大鼠各种内脏器官的血液和组织中形成的顺磁性单核蛋白结合DNIC(М-DNIC)的浓度。与静脉注射奥沙康的相应参数相比,皮下、肌肉或腹腔注射奥沙康时,МАР降低的最大幅度分别从30%到70%不等。另一个差异是,在МАР降低的初始阶段缺乏快速相,并且在肌肉、皮下或腹腔注射奥沙康后,循环血液中形成的蛋白结合M-DNIC持续时间更长。因此,NO供体奥沙康不仅在静脉注射时,而且在肌肉、皮下或腹腔注射时,对大鼠都有明显的降压作用。

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