Сетевой научно-практический журнал СЕРИЯ Медицина и фармация №3

On laboratory animals we investigate endothelio- and cardioprotective effects of enalapril, lozartan and amlodipine at modeling hyperhomocystein induced endothelial dysfunction. It is established that use of ACE inhibitors, blockers of ATI of receptors and calcium channels blockers at the general, expressed endothelio-and cardioprotective action, allows to correct only a number of indicators of functioning an vascular endothelium and cardiovascular system as a whole.

In the result of the performed research, it was discovered that concomitant use of thioctic acid with antioxidant properties and Rosuvastatin (from the class of anticholesterol drugs) had endothelium protective action at the model hypestrogen-L-NAME-induced deficit of nitric oxide consisting in predomination of endothelium-dependent vasodilation and decreasing of endothelial dysfunction factor, as well as in preventing

At the present time much attention is paid to the role and place of L-arginine, a precursor of nitric oxide (NO), in correction of endothelial dysfunction. The purpose of this study is a comparative evaluation of dose-response endothelioprotective effects of small doses of sildenafil (S) and tadalafil (T) in combination with L-arginine (L-arg). The experiments were performed on male rats Wistar. N-nitro-L-arginine methyl ester (L-NAME) was administered i.p. at a dose of 25 mg/kg/day. Conducted following functional vascular test: endothelium dependent vasodilatation (EDV) with acetylcholine, endothelium independent vasodilatation (ENDV) with sodium nitroprusside (NP). The test group of animals (n = 10):I–intact;II–L-NAME;III–L-NAME+S-0,22 mg/kg twice, i.g.;IV–L-NAME+T-0,09 mg/kg i.g., once; V –L-NAME+S+L-arg–200 mg/kg, i.p, once a day; VI –L-NAME+T+L-arg. Hypotensive effect has been identified with the introduction of a low dose of sildenafil in combination with L-arginine, in contrast, there wasn’t observed any significant hypotensive effect with the introduction of tadalafil. We used the index of endothelial dysfunction (IED)-the ratio of calculated indicators-ENDV and EDV. In the group of L-NAME-IED was 5,4±0,6, intact-1,1±0,1,sildenafil-3,2±0,2, tadalafil-2,9±0,1; sildenafil+L-arginine-2,5±0,2;tadalafil+L-arginine-2,1±0,2. The results gained in the research serve in evidence of the effective correction of endothelial dysfunction with sildenafil and tadalafil on L-NAME-induced deficiency of nitric oxide and in reduce doses (in time of 10). The combined use of sildenafil and tadalafil in reduced doses with L-arginine showed an additive endothelioprotective effect.

The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.