Биологические науки/ 8. физиология человека и животных

Dr. Sci. Biol., Prof. Bebyakova N.A., Cand. Biol. Sci. Kuritsin S.N.

Northern State Medical University, Arkhangelsk, Russia

Dysfunction of endothelium blood vessels at sharp stress and her correction of dalargin (D-Ala²-Leu⁵-Arg⁶-enkephalin) not-selective agonist µ- and д- opiate receptors

Stressful loadings are the important reason changing mechanisms of regulation of cardiovascular system. One of the major the stress - limiting of systems of an organism is system of opioid peptides.

Dalargin (D-Ala²-Leu⁵-Arg⁶-enkephalin) - not - selective agonist µ- and д- opiat receptors (ОR) the leu-enkephalin is steady against splitting by enzymes analogue. Now it is used in clinic in quality against ulcers means (it is authorized by Pharmacological committee MZ of the Russian Federation 09.03.82), and also in clinical and experimental researches at various conditions. Dalargin shows practically equal affinity to µ-and д-ОR and does not cooperate with other types ОR. Features dalargins are high insolubility in water and polarity of its molecule that than 20 mg/kg do not allow it to penetrate through hematoencephaly barrier in dozes less. Dalargin modulating influence is established on peripheral vascular resistance in experiment and in clinical researches, that, in opinion of authors, is connected to activation peripheral ОR, located on membranes of endotheliocytes as dalargin in a doze of 0,1 mg/kg will not penetrate through hematoencephaly barrier a barrier. At the same time, cellular mechanisms of regulation of peripheral vascular tone (PVT) of dalargin practically are not investigated.

In this connection the purpose of the given research was studying a role vasoactive endothelial factors - nitrogen oxide (NO) and endothelin-1 (ЕТ-1) in mechanisms of influence not selective activation µ-and д-ОR dalargin on stressful vasoconstriction. During research it was necessary to establish interrelation opioidergic systems and vasoactive endothelial factors in regulation PVT on a background of sharp stress by blockade and activation µ-and д-ОR of dalargin.

Research was carried out on rats of genetic line Wistar by weight of 200-250. Sharp stress modelled a premise of animals in the chamber without rigid fixing within 1 hour. Stressful changes PVT estimated a method of reovasographya, analyzing parameters of an index of peripheral resistance (IPR). Changes of elasticity of vessels estimated on parameters of the module of elasticity (МE) and an index fast fillings by blood (IFB). A level of production NO and ЕТ-1 estimated immunological a method.

During the carried out researches it has been established, that on a background of introduction dalargins in conditions of sharp stress the orientation of changes of parameters PVT coincided with changes at control animals, however stressful growth of the IPR was less expressed, than in the control: on 5-th mines of stress the IPR on 23,3% was lower in comparison with the control (р<0,001), and on 60-th mines of immobilization - is lower 14,6% (р<0,01). In the given conditions less expressed change elastic properties of blood vessels was observed in comparison with the control, and changes were observed at vessels both large, and fine calibre: to 60-th mines of stress МE it was reduced on 28,3% in comparison from 5-th mines of experiment (р<0,001). In comparison with the control the given parameter was higher 39,2% and 47,2% on 5-th and 60-th mines accordingly (р<0,001). Similarly changed and IFB.

Preliminary blockade ОR of naloxon resulted in disappearance of protective effect of dalargin on stressful growth PVT. So on a background of preliminary blockade ОR of naloxon and the subsequent introduction of dalargin the IPR on 5-th mines of experiment on 43,5% was higher, than on a background of introduction of dalargin, to 60-th mines this difference made 37,4% (р<0,001). The given fact testifies that the protective effect of dalargin on stressful vasoconstriction has receptors the nature.

The protective effect of dalargin was accompanied by decrease in level ЕТ-1 on 28,50% (р<0,01) and increase in level NO at 134,0% (р<0,001) in comparison with the control that testifies to their participation in regulation of opioid peptides PVT at sharp stress.

Preliminary blockade NOS of LNNA resulted in disappearance of protective effect of dalargin on stressful growth PVT, substantially removing dalargin-caused increase NO. While on a background not selective blockade receptors of endothelin PD 145,065 and the subsequent introduction of dalargin the total protective effect on stressful vasoconstriction was observed. The received facts testify to leading part NO in protective action of dalargin on stressful vasoconstriction.

Results of research testify to perspectivity of the further studying of dalargin with the purpose of its use for treatment and preventive maintenance stressful changes of the vascular tone caused by infringement of normal functioning of endothelium of blood vessels.

Work is maintained by the grant of the Russian Fund of Basic researches 08-04-98817.