USE OF SELECTIVE INHIBITORS OF ARGINASE 2 AND TADALAFIL IN COMBINED COMPENSATION OF HOMOCYSTEINE-INDUCED ENDOTHELIAL DYSFUNCTION
Use of selective inhibitors of arginase 2 in combination with tadalafil on in the course of modeling of homocysteine-induced endothelial dysfunction provided endotelio- and cardioprotective effects manifested in preventing of SED increase, adrenoreactivity, maintaining myocardial reserve and normalization of the values of biochemical markers (Total NO, expression of eNOS).
Table 1. The effect of selective inhibitors of arginase 2 and tadalafil on dynamics of hemodynamic parameters in animal models of homocysteine-induced endothelial dysfunction (M±m, n=10).
Table 2. The effect of selective inhibitors of arginase 2 and tadalafil on dynamics of contractility parameters in the course of exercise testing in animal models of homocysteine-induced endothelial dysfunction (М±m, n=10).
Table 3. The effect of selective inhibitors of arginase 2 and tadalafil on dynamics of biochemical markers value (TotalNO, eNOS expression) in animal models of homocysteine-induced endothelial dysfunction (М±m, n=10).
Figure 1. Schematic diagram of the effect of arginase in regulation of NO bioavailability and of function of vascular smooth muscle elements.
Hyperactivity of arginase assisted by hydrolysis of L-arginine, ornithine and urea reduces L-arginine availability for NO-synthase (NOS), thus suppressing NO production. Absence of L-arginine will also result in eNOS “uncoupling” so that the enzyme will produce superoxide instead of NO. Generation of superoxide uncoupled with eNOS as well as of NADPH oxidase and peroxynitrite from superoxide and NO will cause the further arginase activity growth. Such changes in the aggregate will reduce NO bioavailability and promote endothelial dysfunction. In smooth muscle vascular cells ornithine favors more intensive formation of L-proline and polyamines which stimulate cells proliferation. Ang II-angiotensin II; BH4, tetrahydrobiopterin; OxLDL, oxidized low-density lipoprotein; LPS, lipopolysaccharide; NADPHox, nicotineamide-adenine dinucleotide phosphate oxidase; NO, nitric oxide; ONOO-peroxynitrite; VSMC, vascular smooth muscle cell.
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Информация для цитирования:
Koklin, I.S. Use of selective inhibitors of arginase 2 and tadalafil in combined compensation of homocysteine-induced endothelial dysfunction / I.S. Koklin // Research result: pharmacology and clinical pharmacology. – 2015. – Vol.1, №1 (1). – P. 13-19. doi: 10.18413/2500-235X-2015-1-4-15-20