Endothelial Nitric Oxide Synthase 4a/B Polymorphism and Its Interaction with Enos G894T Variants in Type 2 Diabetic Pa-tients: Modifying the Risk of Diabetic Nephropathy

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Synthetic Pyridoindole and Rutin Affect Upregulation of Endothelial Nitric Oxide Synthase and Heart Function in Rats Fed a High-Fat-Fructose Diet

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-κB) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-κB expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

The role of ENOS polymorphism (C774T) in the progression of acute peritonitis and the formation of complications

In order to determine the role of ENOS (C774T) gene polymorphism in the progression of acute peritonitis and the formation of complications, a clinical and biochemical study of 40 patients with acute peritonitis was conducted. As a result of the study, it was proved that the early period of acute peritonitis is characterized by the development of endogenous intoxication, intensification of oxidative phenomena, hypercoagulation of the homeostasis system and inhibition of fibrinolysis, and in patients with acute peritonitis, carriers of the pathological TT genotype of the endothelial nitric oxide synthase gene, more pronounced deviations of homeostatic parameters are observed. Key words: acute peritonitis, genotype, DNA diagnostics, genetic testing of genotypes.

Molecular Mechanism of Astragaloside IV in Improving Endothelial Dysfunction of Cardiovascular Diseases Mediated by Oxidative Stress

Endothelial dysfunction, induced by oxidative stress, is an essential factor affecting cardiovascular disease. Uncoupling of endothelial nitric oxide synthase (eNOS) leads to a decrease in nitric oxide (NO) production, an increase in reactive oxygen species (ROS) production, NO consumption, and NO synthesis. As a main active ingredient of astragalus, astragaloside IV can reduce the apoptosis of endothelial cells during oxidative stress. This review is aimed at exploring the mechanism of astragaloside IV in improving oxidative stress-mediated endothelial dysfunction relevant to cardiovascular diseases. The findings showed that the astragaloside IV can prevent or reverse the uncoupling of eNOS, increase eNOS and NO, and enhance several activating enzymes to activate the antioxidant system. In-depth validation and quantitative experiments still need to be implemented.