title: Protection of the vascular endothelium in experimental situations.
abstract: One of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 found in vitro were partly confirmed in vivo. Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effect in vivo.
authors.affiliation: Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Ružena
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authors.lastname: Sotníková
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authors.lastname: Nedelčevová
authors.forename: Jana
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authors.lastname: Navarová
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authors.lastname: Nosáĺová
authors.forename: Katarína
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authors.lastname: Drábiková
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authors.lastname: Szöcs
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authors.lastname: Kyseĺová
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authors.lastname: Bezek
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authors.lastname: Knezl
authors.forename: Ján
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authors.lastname: Dřímal
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authors.lastname: Brosková
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authors.forename: Ludmila
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authors.lastname: Okruhlicová
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authors.lastname: Bernátová
authors.forename: Viktor
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authors.lastname: Bauer