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

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• 作者：Alexander А. Тimoshin^a ; Vladimir L. Lakomkin^a ; Alexander А. Аbramov^a ; Enno K. Ruuge^a ; Valery I. Kapel&rsquo ; ko^a ; Evgeny I. Chazov^a ; Anatoly F. Vanin^b ; ^{vanin@polymer.chph.ras.ru" class="auth_mail" title="E-mail the corresponding author}
• 关键词：B- or M-DNIC ; binuclear or mononuclear dinitrosyl iron complexes ; BSA ; blood serum albumin ; GS&ndash ; NO ; S-nitrosoglutathione ; IM ; intramuscular ; IP ; intraperitoneal ; IV ; intravenous ; MAP ; mean arterial pressure ; PRect ; rectal ; SubCut ; subcutaneous ; SDS ; sodium dodecyl sulfate
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：765
• 期：Complete
• 页码：525-532
• 全文大小：1321 K

文摘

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.