Медицина/6. Экспериментальная и клиническая фармакология

Saroyan K.V.², Full Prof. Pokrovsky M.V.¹, Sytnik M.V.², MD Pokrovskaya T.G.¹, MD Korokin M.V.¹, PhD Gudyrev O.S.¹, PhD Denisyuk T.A¹, Losenok P.I.², MD Losenok S.A.², PhD Arustamova A.A.¹, PhD Kotelnikova L.V.², PhD Titareva L.V.², MD Kochkarov V.I.¹.

¹Federal State Autonomous Institution of Higher Professional Education "Belgorod State National Research University", Russia

²State Educational Institution of Higher Professional Education "Kursk State Medical University", Ministry of Health, Russia

Dose-dependent endothelio-, cardioprotective effects of rosuvastatin in experiment

HMG-Co-A reductase inhibitors are currently being considered as priority group of drugs with pleiotropic endothelioprotective activity [1, 2, 5, 6]. The purpose of this study is to conduct a complex study of endothelio- and cardioprotective effects of inhibitor of HMG-Co-A reductase rosuvastatin in modeling L-NAME-induced endothelial dysfunction (ED).

Experiments were carried out on white male rats Wistar weighing 250-300 g N-nitro-L-arginine methyl ester (L-NAME) was administered daily once a day, intraperitoneally, at a dose of 25 mg/kg/day. On day 8 of the experiment, under anesthesia (chloral hydrate 300 mg/kg) was recorded blood pressure (BP), being the introduction of pharmacological agents (acetylcholine (ACh) at a dose of 40 mg/kg, sodium nitroprusside (NP) in a dose of 30 mg/kg) into the right femoral vein. The degree of ED in experimental animals, as well as the degree of correction of the study medication was assessed by the estimated coefficient of ED (CED) [3, 4]. CED is the ratio of the area of the triangle above the curve restoration of blood pressure in response to the NP to the area of the triangle above the curve of blood pressure reduction in response to the ACh. Hemodynamic parameters were measured continuously by means of sensors and complex TSD104A MP100, production Biopac System, Inc., USA. Myocardial stress tests conducted on adrenoreactivity and load resistance. Biochemical marker of ED served and the level of C-reactive protein (CRP) Total NO. Rosuvastatin was administered intraperitoneally at doses of 0.86 and 1.7 mg / kg.

CED values were 1,2 ± 0,1 in the group of intact animals and 5,3 ± 0,5 in the group with ED. Rosuvastatin dose-dependently prevented the increase in CED, the value of which amounted to 2,8 ± 0,2 and 1,5 ± 0,5 (p <0.05). In parallel, dose-dependently prevented by reducing the concentration of nitrite ions. Most striking was the dynamics of CRP. In the group with ED going to a significant increase (0,38 ± 0,1 mg/l) compared to intact animals. Rosuvastatin at both doses reduced the value lower than the control group to 0,14 ± 0,02 and 0,13 ± 0,02 mg/l (p <0.05). Results of stress tests also showed a dose-dependent protective effect of rosuvastatin, which is expressed in preventing increase of adrenoreactivity, improve contractility indices during the load test resistance.

Conclusions. Rosuvastatin has expressed dose-dependent endothelio- and cardioprotective effects in the simulation of ED, one of the possible mechanisms is anti-inflammatory effect which is accompanied by a decrease of CRP.

Thus, HMG-Co-A reductase inhibitor rosuvastatin showed pronounced dose-dependent endothelio- and cardioprotective effects in the model of L-NAME-induced endothelial dysfunction.

The study was supported by a grant of the President of the Russian Federation № MK-905.2012.4.

The study was conducted as part of the state task for R & D (State Contract № 4.913.2011).

References:

1. Atroshchenko E. Pleiotropic effects of statins: a new aspect of the HMG-CoA reductase / / Medical News. – 2004. - № 3. - P. 59-66.

2. Effect of L-arginine, vitamin B6 and folic acid on indices of endothelial dysfunction and the microcirculation in the placenta in modeling L-NAME-induced deficiency of nitric oxide / MV Korokin, MV Pokrovsky, OO Novikov et al / / Bulletin of Experimental Biology and Medicine. - 2011. - Vol. 152. - № 7. - P. 77-80.

3. Pokrovsky MV, VI Kochkarov, TG Pokrovskaya, et al. A new look at the correction of endothelial dysfunction / / Russian Journal of Immunology.- 2006. - Vol.9.- P. 60-61.

4. Pokrovsky, MV Methodological approaches to quantify the development of endothelial dysfunction in L-NAME-induced deficit model of nitric oxide in the experiment / M.V.Pokrovsky, VI Kochkarov, T.G.Pokrovskaya et al. / / Kuban Scientific Medical Journal. - 2006.- №10.- P.72-77.

5. Realities and perspectives of pharmacological correction «ADMA-eNOS"-associated pathways in preeclampsia / MV Pokrovsky, N. Filippenko, M. Korokin et al. / / Rational pharmacotherapy in cardiology. - 2010. - № 6. - P. 882-887.

6. Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction / MV Pokrovskiy, M.V. Korokin, S.A. Tsepeleva et al. / / International Journal of Hypertension. - 2011. - Vol. 2011 (2011). - Article ID 515047, 4 pages, doi: 10.4061/2011/515047.