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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 ä- 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 ä- opiat receptors
(ÎR) 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 ä-ÎR
and does not cooperate with other types ÎR. 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 ÎR, 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 (ÅÒ-1) in
mechanisms of influence not selective activation µ-and ä-ÎR 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 ä-ÎR 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 (ÌE) and
an index fast fillings by blood (IFB). A level of production
NO and ÅÒ-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 (ð<0,001), and on 60-th mines of immobilization - is lower 14,6% (ð<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 ÌE it
was reduced on 28,3% in comparison from 5-th mines of experiment (ð<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 (ð<0,001).
Similarly changed and IFB.
Preliminary
blockade ÎR of naloxon resulted in
disappearance of protective effect of dalargin on stressful growth PVT. So on a background of preliminary blockade ÎR 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% (ð<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 ÅÒ-1 on
28,50% (ð<0,01) and increase in level NO at
134,0% (ð<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.