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Abstract

Background: Endothelial dysfunction (ED) is one of the most cardiovascular disease pathogenesis leaders. This fact discloses a large number of potential molecular targets for novel pharmacological drugs. Among these targets, enzymes arginase type II and phosphodiesterase type 5 can be distinguished. Materials and Methods: The study included 120 male Wistar rats weighting 250–300 g, which were randomly divided into 12 equal groups. The screening was carried out among compounds with laboratory codes C239–0844, L207–0208, L207–0210, L207–0322, L207–0404, L207–0525, and L327–0346. N-nitro- L-arginine methyl ether (L-NAME)-induced ED was modeled by daily intraperitoneal injection of L-NAME at a dose of 25 mg/kg to male rats for 7 days. The degree of coefficient of ED (CED) was determined on the 8th day from the beginning of the experiment. In parallel, a test was performed for adrenoreactivity and myocardial reserve exhaustion, as well as an assessment of the values of biochemical markers (total nitric oxide [NO] and endothelial NO synthase [eNOS] expression). Results and Discussion: Compounds L207–0525 and L327–0346 at a dose of 1 mg/kg showed the highest activity and were showing the values of CED 1.5 ± 0.3 and 1.9 ± 0.4 c.u., respectively, whereas in the control, it was 5.4 ± 0.4 c.u. At the same time, studied compounds showed cardioprotective effect, what expressed in adrenoreactivity decrease and myocardial reserve exhaustion, as well as a lowering of NO metabolites (NOx) values and expression of eNOS. The combined use of tadalafil and arginase II inhibitors increased the endothelioprotective effect but did not enhance the cardioprotective effect. Conclusion: The study proved the possibility of arginase inhibitors using to prevent the ED development. Among arginase II inhibitors, the most promising compounds are L207–0525 and L327–0346.

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	JPR Solutions

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