Functional nitric oxide conjugate systems state/restored heart thiols of rats in modeling isadrine-pituitrin's myocardial infarction using metabolite-tropic cardioprotector “Angiolin”

Abstract

According to modern researches, endothelial dysfunction (ED) is one of the primary pathogenetic elements of cardiovascular diseases (myocardial infarction [MI], ischemic heart diseases, cerebral ischemic stroke, atherosclerosis, arterial hypertension, pulmonary hypertension, heart failure, dilated cardiomyopathy) as well as obesity, hyperlipidemia, diabetes and hyperhomocysteinemia. 1,3 The main mechanism underlying ED is the decrease of nitric oxide (NO) formation and bioavailability at simultaneous level increase of superoxide anion and of potent vasoconstrictor's production, and the decrease of energy products in endotheliocytes. 2,3,13,14,16,17 Consequently, ABSTRACT Background: According to modern researches, endothelial dysfunction (ED) is one of the primary pathogenetic elements of cardiovascular diseases (myocardial infarction [MI], ischemic heart diseases, cerebral ischemic stroke, atherosclerosis, arterial hypertension, pulmonary hypertension, heart failure, and dilated cardiomyopathy) as well as obesity, hyperlipidemia, diabetes and hyperhomocysteinemia. The aim of this work was to study the infl uence of potential metabolitotropic cardioprotector "Angiolin" on the parameters of conjugate systems nitric oxide (NO)/restored thiols in heart under isadrine-pituitrin MI. Methods: This study was performed on Wistar white rats weighing 190-210 g. Biochemical, immune-enzyme analysis and histoimmunechemical study were performed. Results: In histological sections of hearts of the rats receiving Angiolin in parenteral dosing 50 mg/kg 30 mins before each pituitrin injection the density of endothelial NOsynthase (NOS)-positive cells increased by 29% and the density of inducible NOSpositive cells decreased by 23.3%. In cytosolic fraction of myocardium homogenate NOS activity increased by 27%, the concentration of NO stable metabolites increased by 70% and the content of nitrosative stress marker nitrotyrosine decreased by 42% when compared with control group. At the same time in similar samples of heart homogenate the increase of restored thiol groups' level by 53.3%, methionine-by 35.1%, cysteine-by 170% and activity of glutathione reductase-by 186% was noted. The administration of reference drug mildronate to the animals with MI in dose 100 mg/kg did not result in signifi cant changes of the studied parameters of thiol-disulfi de system and NO system of the heart when compared with control group. Conclusions: Angiolin does not infl uence directly on NOS in MI, but at the same time protects NO from nitrosative stress increasing restored equivalents of thioldisulfi de system.

The Cardio- and Neuroprotective Effects of Corvitin and 2-Oxoglutarate in Rats with Pituitrin-Isoproterenol-Induced Myocardial Damage

“…The rat model of isoproterenol-induced myocardial injury serves as a well-accepted standardized model for the evaluation of several cardiac dysfunctions and for studying the efficacy of various natural and synthetic cardioprotective agents [ 33 – 35 ]. We used the model proposed by Belenichev and others [ 36 ], which follows the principle that the imbalance between the supply and the metabolic demand of oxygen by the heart muscle is achieved by the combined administration of pituitrin and isoproterenol. The drugs were administered as follows: first, pituitrin (0.5 U/kg)—intraperitoneally, followed by isoproterenol after 20 minutes (100 mg/kg)—subcutaneously.…”

Altered Blood Molecular Markers of Cardiovascular Function in Rats After Intrauterine Hypoxia and Drug Therapy

“…The effect of intrauterine hypoxia on eNOS expression depends on the duration of hypoxia, since an increase in ROS production can impair NO bioavailability and suppress eNOS expression [1,20,29] The dynamics of the relationship between ROS and NO determines vascular tone, since the hypoxia-induced increase in ROS and, consequently, the ROS/NO ratio in the fetus enhances peripheral vasoconstriction and increased myocardial ischemia. An excess of NADPH during prenatal hypoxia is the cause of the formation of ROS, which can react with NO to form a stable peroxynitrite anion, reducing the bioavailability of NO [12]. The revealed decrease in eNOS expression during a significant increase in the level of nitrotyrosine in both 1 and 2 month old rats after intrauterine hypoxia may indicate in favor of the formation of endothelial dysfunction in these animals.…”

“…Thiotriazoline (morpholinium 3-methyl-1,2,4-triazolyl-5thioacet) is a specific scavenger of NO and its cytotoxic forms, increases the bioavailability of NO, protecting it from ROS. Thiotriazoline under conditions of ischemia enhances the compensatory activation of the malate-aspartate shuttle mechanism, reduces the inhibition of oxidation processes in the Krebs cycle while maintaining the intracellular ATP pool, exhibits hepato-, cardioprotective, anti-ischemic and antioxidant properties [10,11,12].…”

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

“…L-lysine 3-methyl-1,2,4-triazolyl-5-thioacetate Angiolin (L-lysine 3-methyl-1,2,4-triazolyl-5-thioacetate) exhibits anti-ischemic, antioxidant properties. It is known that L-lysine can be transformed in the body into pipecolic acid, which increases the affinity of GABA-benzodiazepines-receptor complex and reduces glutamate excitotoxicity (Belenichev et al, 2015b;Nagornaya et al, 2015;Kucherenko et al, 2018a; Figure 4). The mechanism of this action of Angiolin may be associated with its effect on the level of HSP70.…”