UDC

615.22:612.14.085.1

Authors

Bebyakova Natalya Aleksandrovna
Northern State Medical University (Arkhangelsk, Russia)
Levitsky Sergey Nikolaevich
Northern State Medical University (Arkhangelsk, Russia)
Khromova Anna Vladimirovna
Northern State Medical University (Arkhangelsk, Russia)
Komandresova Tatyana Mikhailovna
Pskov State University (Pskov, Russia)
Shabalina Irina Alekseevna
State University (Pskov, Russia)

Abstract

The paper presents the results of an experimental study into the effect of selective μ-opioid DAGO receptor agonist on blood pressure and peripheral vascular tone in Wistar rats under one hour’s immobilization. We evaluated blood pressure and peripheral vascular tone by tetrapolar rheography of rat tail artery using “Diastom-01” multifunctional diagnostic complex. Immobilization in rats was accompanied by 129.0 % higher level of corticosterone than that in intact animals. Activation of μ-opiate DAGO receptors under acute stress resulted in fewer stress-related changes in the cardiovascular system. By the end of immobilization at DAGO intake, the systolic pressure was 13.2 % and the diastolic one – 22.6 % lower compared to the control series. The peptide’s best normalizing effect was produced on the peripheral vascular tone, most likely due to the direct stimulation of peripheral μ-opioid receptors by the preparation. The insignificant rise in average dynamic blood pressure during DAGO intake indicates optimization of cardiovascular system functioning under emotional stress. At DAGO intake, the peripheral resistance index was 22.0 % lower than the control figures. The peptide’s protective effect was expressed in inhibition of stress-related increase in peripheral vascular tone and higher elasticity of blood vessels, the changes mostly concerning large vessels.

Keywords

opioid receptors, DAGO, blood pressure, peripheral vascular tone, vasoconstriction, immobilization

References

1. Dmitriev A.D. Biosintez neyropeptidov [Biosynthesis of Neuropeptides]. Itogi nauki i tekhniki. Ser.: Farmakologiya. Khimioterapevticheskie sredstva. T. 13. Opioidnye peptidy i ikh retseptory [Scientific and Technical Results. Ser.: Pharmacology. Chemotherapeutic Agents. Vol. 13. Opioid Peptides and Their Receptors]. Moscow, 1982, pp. 7–49. 
2. Maslov L.N., Lishmanov Yu.B., Smagin G.N. Opioidnye retseptory. Sostoyanie, problemy, perspektivy [Opioid Receptors: State of the Art and Prospects in Research]. Eksperimental’naya i klinicheskaya farmakologiya, 2002, vol. 65, no. 2, pp. 70–75. 
3. Gromov L.A., Krivorotov S.V. Lokalizatsiya opiatnykh retseptorov na vnutrenney poverkhnosti kletochnoy membrany [Localization of Opioid Receptors on the Inner Surface of Cell Membranes]. Fiziologicheskiy zhurnal SSSR im. I.M. Sechenova, 1991, vol. 76, no. 3, pp. 126–129. 
4. TAN-67, a Delta 1-Opioid Receptor Agonist, Reduces Infarct Size Via Activation of Gi/o Proteins and KATP Channels. Am. J. Physiol., 1998, vol. 274, no. 3, pt. 2, pp. 909–914. 
5. Znachenie opioidnykh retseptorov v regulyatsii tolerantnosti serdtsa k patogennomu deystviyu dlitel’noy ishemii / reperfuzii in vivo [Significance of Opioid Receptors in Regulation of Cardiac Tolerance in Pathogenic Impact of Long- Term Ischemia-Reperfusion in Vivo]. Rossiyskiy fiziologicheskiy zhurnal im. I.M. Sechenova, 2009, vol. 95, no. 6, pp. 563–572. 
6. Ustoychivost’ miokarda k ishemicheskim i reperfuzionnym povrezhdeniyam pri khronicheskom vvedenii agonistov i antagonistov opioidnykh retseptorov [Myocardial Resistance to Ischemic and Reperfusion Injuries Under Conditions of Chronic Administration of Opioid Receptor Agonists and Antagonists]. Byulleten’ eksperimental’noy biologii i meditsiny, 2008, vol. 145, no. 6, pp. 642–644. 
7. Handa B.K., Lane A.C., Lord J.A.H., et al. Analogues of β-LPH61–64 Possessing Selective Agonist Activity at μ-Opiate Receptors. Eur. J. Pharmacol., 1981, vol. 70, no. 4, pp. 531–540. 
8. Pshennikova M.G. Fenomen stressa. Emotsional’nyy stress i ego rol’ v patalogii [The Stress Phenomenon. Emotional Stress and Its Role in Pathology]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2000, no. 2, pp. 24–31. 
9. Pshennikova M.G. Rol’ opioidnykh peptidov v reaktsii organizma na stress [The Role of Opioid Peptides in the Body’s Response to Stress]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 1987, no. 3, pp. 85–89. 
10. Lishmanov Yu.B., Maslov L.N. Opiatergicheskaya regulyatsiya sostoyaniya tsentral’noy gemodinamiki [Opioid Regulation of Central Hemodynamics]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2003, no. 1, pp. 2–11. 
11. Sudakov K.V. Individual’nost’ emotsional’nogo stressa [Individuality of Emotional Stress]. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova, 2005, no. 2, pp. 4–12. 
12. Shabalina I.A. Modulyatsiya stressornoy vazokonstriktsii pri sochetannoy aktivatsii μ- i δ-opiatnykh retseptorov agonistami s razlichnoy stepen’yu stabil’nosti: dis. … kand. biol. nauk [Modulation of Stress Vasoconstriction at Combined Activation of μ- and δ-Opioid Receptors by Agonists with Varying Stability Degrees: Cand. Biol. Sci. Diss.]. Arkhangelsk, 2012. 117 p. 
13. Loginova N.K. Funktsional’naya diagnostika v stomatologii [Functional Diagnosis in Dentistry]. Moscow, 1994. 88 p. 
14. Sokolova I.V. Otsenka lokal’noy fraktsii serdechnogo vybrosa s pozitsiy dvukhfaznoy modeli mekhanizma pul’sovoy gemodinamiki [Estimation of the Local Fraction of Cardiac Output Using a Two-Phase Model of Pulsatile Hemodynamics]. Fiziologiya cheloveka, 2006, vol. 32, no. 2, pp. 72–79. 
15. Metodika otsenki funktsional’nogo sostoyaniya serdechno-sosudistoy sistemy melkikh laboratornykh zhivotnykh s pomoshch’yu diagnosticheskogo komp’yuternogo kompleksa “Diastom-01” [Methods of Assessing the Functional State of the Cardiovascular System of Small Laboratory Animals Using the Diagnostic Computer Complex “Diastom-01”]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2002, no. 1, p. 25. 
16. Zagryadskiy V.P., Sulimo-Samuylo Z.K. Metody issledovaniya v fiziologii truda [Research Methods in Work Physiology]. Leningrad, 1976, pp. 26–38. 
17. Rosen M.R. Antiarrhythmic Drugs. Mechanisms of Antiarrhythmic and Proarrhythmic Actions. New York, 1995, pp. 393–404. 
18. Aleksandrova E.A. Kal’tsiytransportiruyushchie sistemy i regulyatsii kontsentratsii kal’tsiya v kardiomiotsitakh [Calcium Transport Systems and Regulation of Calcium Concentration in Cardiomyocytes]. Uspekhi fiziologicheskikh nauk, 2001, no. 3, pp. 40–48. 
19. Norman R.I. Textbook of Hypertension. Oxford, 1994, pp. 120–128. 
20. Lasukova T.V., Rebrova T.Yu. Aktivatsiya μ-opiatnykh retseptorov i ustoychivost’ kardiomiotsitov k svobodnoradikal’nomu povrezhdeniyu [Activation of μ-Opioid Receptors and Cardiomyocyte Resistance to Free Radical Damage]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2001, no. 2, pp. 15–17. 
21. Meerson F.Z. Patogenez i preduprezhdenie stressornykh i ishemicheskikh povrezhdeniy serdtsa [Pathogenesis and Prevention of Stress and Ischemic Heart Damage]. Moscow, 1984. 265 p. 
22. Drozdova G.A. Kletochnye mekhanizmy arterial’noy gipertenzii [Cellular Mechanisms of Arterial Hypertension]. Patologicheskaya fiziologiya i eksperimental’naya terapiya, 2000, no. 3, pp. 26–30.