Biopolym. Cell. 2022; 38(3):145-157.
http://dx.doi.org/10.7124/bc.000A79
Reviews
Nitric oxide-dependent mechanism of endothelial dysfunction formation is a promising target link for pharmacological management
1Belenichev I. F., 1Bak P. G., 1Popazova O. O., 1Bukhtiyarova N. V., 2Yadlovsky O. E.
  1. Zaporizhia State Medical University
    26, Mayakovsky avenue, Zaporizhzhia, Ukraine, 69035
  2. Institute of Pharmacology and Toxicology of National Medical Academy of Science of Ukraine
    14, Anton Tsedyk Str., Kyiv, Ukraine, 03057

Abstract

Herein, we presented a review to show that the main mechanism underlying endothelial dysfunction is a decrease in the formation and bioavailability of NO against the background of inhibition of eNOS expression and reduced equivalents of the thiol-disulfide system with a simultaneous increase in the levels of cytotoxic forms of NO and the production of powerful vasoconstrictors. Based on the foregoing, the conjugated systems eNOS-L-arginine-NO/SH can be undoubtedly claimed in the near future as a promising target for the pharmacological correction of endothelial dysfunction. Since it is a nitrosative stress that plays the role in the development of endothelial dysfunction, it is topical to search for potential endothelial protectors in the series of S-substituted 1,2,4-triazole, which have the properties of antioxidanitts and NO scavengers. A striking representative of this cohort is Thiotriazolin which is a drug with cardioprotective, anti-ischemic and antioxidant properties, though does not possesses endothelial protective activity. As a result of chemical modification of the molecule of the latter, we obtained the compound (S)-2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate (Angiolin), which manifests endothelium-protective properties against the background of cardio-protective, anti-ischemic and antioxidant activities.
Keywords: endothelial dysfunction, NO, nitrosative stress, reduced thiols, S-derivatives of 1,2,4-triazole
Full text: (PDF, in English)

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