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.

Consequences of lipopolysaccharide and n-3 polyunsaturated fatty acid administration on aortic function of spontaneously hypertensive rats

“…Oxidative stress is involved in atherogenesis, which is initiated by endothelial injury in cases with cardiovascular risk factors, including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome (Husain et al 2015;Salmanoglu et al 2016). Participation of oxidative stress in induction of endothelial dysfunction was confirmed by the beneficial action of antioxidants which were able to suppress the detrimental effect of reactive oxygen species (Sotníková et al 2008(Sotníková et al , 2011. Results of Requintina and Oxengruk (2003) indicated that the effect of LPS on lipid peroxidation is dose-, time-, and species-dependent.…”

Comparison of two fluid solutions for resuscitation in a rabbit model of crush syndrome

“…ESM-1 level was significantly elevated in the model group, which is also regulated by proinflammatory cytokines. The serum ESM-1 level was normal in healthy subjects, whereas the serum ESM-1 level was significantly increased in patients with acute and severe sepsis [30]. Resuscitation using 6 % HES 130/0.4 ?0.9 % saline played a role in suppressing the inflammatory response and also led to a restored tendency of ESM-1 level compared to the model group.…”

Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration

“…Further significant property of SMe1EC2 was its ability to protect endothelium under conditions of experimental diabetes of rats. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of nitric oxide in the aorta (Sotníková et al, 2011 ). Overall, the compound attenuated endothelial injury in diabetic animals.…”