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PHARMACOLOGICAL EFFICACY OF AN INHIBITOR OF ARGINASE-2 KUD975 WITH L-NAME-INDUCED ENDOTHELIAL DYSFUNCTION

The study of endotelio- and cardioprotective activity of finished dosage forms - tablets, film-coated, containing 10 mg of phenolic nature KUD-975, was shown a statistically significant decrease in blood pressure and the coefficient  of endothelial dysfunction on the background of simulation L-NAME-induced pathology. In the group of animals treated with KUD975 found a statistically significant increase in the concentrations of stable metabolites of nitric oxide, which in addition to the normalization of vasodilation says about endothelioprotektive action of the compounds studied. The initial values of the functioning of the left ventricle of the heart during treatment with KUD975 found hypodynamic action, which resulted in a decrease in the absolute values of the heart left ventricle pressure, + dp / dt, -dp / dt. Results of the study of the functional state of the myocardium during exercise testing, and histological evaluation of the myocardium revealed distinct cardioprotective effects in the study of KUD975 at a dose of 3 mg / kg, expressed in preventing the increase adrenoreactivity, exhaustion myocardial reserve during the sample to the load resistance and hypodynamic restructuring physiological response to the report on hypoxia / reoxygenation compared with animals that have modeled the endothelial dysfunction.

Иллюстрации

 

Figure 1. Effect of KUD975 on blood pressure in modeling endothelial dysfunction (mmHg, N = 10 animals in the group).

Notes: here and below

1 * - p <0,05 - in comparison with the group of intact animals;

2 ** - - p <0.05 - in comparison with the group of animals that received L-NAME

1 - Intact animals; 2 –L-NAME; 3 – L-NAME + KUD975

Figure 2. The values of the coefficient of endothelial dysfunction in the simulation of L-NAME induced deficiency of nitric oxide and its correction with the help of the developed KUD975 (standard units, N = 10 animals in the group).

  1. Intact animals; 2 –L-NAME; 3 – L-NAME + KUD975

Figure 3. Influence of the developed KLGF KUD975 on eNOS expression (% Of control, N = 10 animals per group).

1- Intact animals; 2 – L-NAME; 3 – L-NAME + KUD975;

Figure 4. Effect of test compounds on the concentration of stable metabolites of nitric oxide (NOx) (μmol / L, N = 10 animals in the group).

1- Intact animals; 2 – L-NAME; 3 – L-NAME + KUD975

Table 1 - Changes in the ratios of left ventricular contractility of the rat heart in the modeling of L-NAME induced endothelial dysfunction and its correction with the help of KUD975 (M ± m).

Figure 5 Effect of KUD975 on the maximum arterial pressure in the cavity of the left ventricle of the heart when carrying out a sample for adrenoreactivity. (Mm Hg, N = 10 animals per group).

1- Intact animals; 2 – L-NAME; 3 – L-NAME + KUD975

Figure 6 Effect of the KUD975 GLF on the depletion of the myocardial reserve when carrying out the sample on the resistance load (%, N = 10 animals in the group).

1- Intact animals; 2 – L-NAME; 3 – L-NAME + KUD975

Table 2 - Changes in the ratios of left ventricular contractility in rat hearts in a sample with acute hypoxia and reoxygenation in the modeling of L-NAME-induced endothelial dysfunction and its correction with the help of  KUD975 tablets (M ± m)

 Figure 7. Histological structure of the myocardium in animals receiving KUD975 at a dose of 3 mg / kg on day 8 of the experiment: a homogeneous structure of the myocardium with a uniform blood filling of capillaries between cardiomyocytes, moderately pronounced dilatation and plethora of venules in the subepicardial zone (B). X200.

DOI: 10.18413/2500-235X-2017-3-1-10-17
Количество просмотров: 2086 (смотреть статистику)
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