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Change of Parameters of Functioning of the Cardiovascular and Respiratory Systems in Rats of Different Ages under Effects of Low Doses of the Cholinesterase Inhibitor Phosphacol

  • Comparative and Ontogenic Physiology
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Abstract

In the 4-day old rat pups and adult animals there were studied effects of subacute and acute phosphacol intoxication at the doses producing and not producing inhibition of aetylcholinesterase on ECG parameters and respiration rate. Analysis of the heart rhythm variability (HRV) was performed using an original program designed in the Labview media. The frequency diapason of cardiointervals was divided as follows: the high-frequency component (HF)-0.8-2.5 Hz, the low-frequency (LF, waves of the II order)-0.8-0.3 Hz; frequencies lower than 0.3 Hz-VLF (slow waves of the III order). Under the conditions of the subacute intoxication the heart rate frequency in the 4-day old and in adult rats increases by 36% and 13%, respectively, the respiration rate frequency increases by 73% in the newborn and does not change in adult rats. The VHR analysis indicates an increase of the tone of the parasympathetic nervous system. The level of the sympathetic activity somewhat increases in adults, but decreases in the 5-day old rat pups, which leads to an essential shift of the vagosympathetic balance towards predominance of parasympathetic influences. In adult rats, unlike the newborns, the role of the humoral-metabolic factors in regulation of the cardiac rhythm and vasomotor reactions increases significantly. Remarkably, the decrease of the nervous sympathetic effects in the rat pups leads to the positive chronotropic effect and stabilization of the cardiac rhythm. Acute phosphacol intoxication (doses of 0.25 and 1 µg/kg) is studied in the 4-day old rat pups. The low dose of the drug leads to development of a moderate bradycardia without disturbances of the cardiac rhythm. The high phosphacol dose produces pronounced bradycardia; on its background there develops a long-term transitory arrhythmia representing complexes of the heart rhythm, which alternate in the decasecond or nearminute rhythm and are separated by periodicity that is one order slower. We observed such rhythm earlier during activation of central N-cholinoreactive structures and development of bilateral pneumothorax. Results of the present study allow stating the paradoxical heart rhythm not as agonic, non-peculiar to the “living” organism, but as a special form of functioning of cardiac pacemakers due to disturbances of the heart regulatory mechanism.

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REFERENCES

  1. Rosanova, V.D., Ocherki po experimental’noi vozrast-noi farmakologii (Essays of Experimental Age Pharmacology), Leningrad, 1968.

  2. Sorimachi, M. and Kataoka, K., High Affinity Choline Uptake: An Early Index of Cholinergic Innervation in Rat Brain, Brain Res., 1975, vol. 94, pp. 325–336.

    Article  CAS  PubMed  Google Scholar 

  3. Vijayan, V.K., Distribution of Cholinergic Neurotransmitter Enzymes in the Hippocampus and the Dentate Gyrus of the Adult and Developing Mouse, Neurosci., 1979, vol. 4, pp. 121–137.

    Article  CAS  Google Scholar 

  4. Lavreneva, S.M., Nalivaeva, N.N., and Zhuravin, I.A., Activity of Cholinesterase of the Sensomotor Cortex in Early Ontogenesis of Rats Exposed to Prenatal Hypoxia, Zh. Evol. Biokhim. Fiziol., 2003, vol. 39, pp. 154–159.

    CAS  PubMed  Google Scholar 

  5. Zhuravin, I.A., Formation of Central Mechanisms of Regulation of Mammalian Motor Functions Depending on Conditions of Embryonal Development, Zh. Evol. Biokhim. Fiziol., 2002, vol. 38, pp. 478–484.

    CAS  PubMed  Google Scholar 

  6. Coyle, J.T. and Yamamura, H.I., Neurochemical Aspects of the Ontogenesis of Cholinergic Neurons in the Rat Brain, Brain Res., 1976, vol. 18, pp. 444–447.

    Google Scholar 

  7. Kotas, F.M. and Prince, A.K., High Affinity Uptake of Choline, a Marker for Cholinergic Terminals, is not Specific in Developing Rat Brain, Develop. Brain Res., 1987, vol. 35, pp.175–181.

    Article  CAS  Google Scholar 

  8. Raevskii, V.V., Ontogenez mediatornykh sistem mozga (Ontogenesis of the Brain Transmitter System), Moscow, 1991.

  9. Belgova, I.N., Markova, I.V., and Tatarintseva, A.N., Age Differences in Reaction of the Rat Intestine Smooth Muscle to Acetylcholine and Cholinomimetic Drug, Vseros. Symposium “Fiziologicheskaya rol’mediatorov” (All-Russia Symposium “Physiological Role of Transmitters”), Kazan, 1972, p. 19.

  10. Buznikov, G.A., Neirotransmittery v embriogeneze (Neurotransmitters in Embryogenesis), Moscow, 1987.

  11. Mikhelson, M.Ya. and Zeimal, E.V., Atsetilkholin (Acetylcholine), Leningrad, 1970.

  12. Appleyard, M.E., Non-Cholinergic Function of the Acetylcholinesterase, Biochem. Soc. Trans., 1994, vol. 22, pp. 749–755.

    CAS  PubMed  Google Scholar 

  13. Contestabile, A., Histochemical Characterization of Cholinesterase Activity in the Frog Brain with Special Reference to its Localization on the Wall Blood Vessel, Histochen. J., 1976, vol. 8, pp. 513–521.

    Article  CAS  Google Scholar 

  14. Lan, C.T., Shieh, J.Y., Wen, C.Y., Tan, C.K., and Ling, E.A., Ultrastructural Localization of the Acetylcholinesterase and Choline Acetyltransferase in Oligodendrocytes, Glioblasts and Vascular Endothelial Cells in the External Cuneate Nucleus of the Gerbil, Anat. Embryiol. (Berlin), 1996, vol. 194, pp. 177–185.

    CAS  Google Scholar 

  15. Skopichev, V.G., Prozorovskii, V.B., and Medvedeva, S.B., Participation of Distant Cholinergic Mechanism in Blood Vessels Reaction on Organophosphate Inhibitors of Cholinesterase, Morphologiya (Moscow), 2000, vol. 117, no.4, pp. 66–69.

    Google Scholar 

  16. Buonassisi, V. and Venter, J.C., Hormone and Neurotransmitter Receptors in an Established Vascular Endothelial Cell Line, Proc. Natl Acad. Sci. USA, 1976, vol. 73, pp. 1612–1626.

    CAS  PubMed  Google Scholar 

  17. Furchgott, R.F. and Zavadski, J.V., The Obligatory Role of Endothelial Cells in the Relaxation of Arterial Smooth Muscle by Acetylcholine, Nature, 1980, vol. 288, No.5789, pp. 373–376.

    CAS  PubMed  Google Scholar 

  18. Chand, N. and Altura, B.M., Acetylcholine and Bradykinin Relax Intrapulmonary Arteries by Acting on Endothelial Cells; Role in Lung Vascular Diseases, Science, 1981, vol. 213, no.4514, pp. 1376–1379.

    CAS  PubMed  Google Scholar 

  19. Akselrod, S., Gordon, D., and Ubel, F.A., Power Spectrum Analysis of Heart Rate Fluctuation: a Quantative Probe Beat-To-Beat Cardiovascular Control, Science, 1981, vol. 213, no.4504, pp. 220–222.

    CAS  PubMed  Google Scholar 

  20. Baevskii, R.M., Kirillov, O.I., and Kletskin, S.Z., Matematichesii analiz serdechnogo ritma pri stresse (Mathematical Analysis of the Cardiac Rhythm in Stress), Moscow, 1984.

  21. Baevskii, R.M. and Ivanov, G.G., Variability of the Cardiac Rhythm: Theoretical Aspects and Possibilities of the Clinical Application (http://www.ecg.ru/books/book03/g15.html).

  22. Ellman, G.L., Courthey, D.K., Andres, V., and Featherstone, R.M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochem. Pharmacol., 1961, vol.7, pp.88–95.

    CAS  PubMed  Google Scholar 

  23. Kasparov, S. and Paton, J.F.R., Changes in Baroreceptor Vagal Reflex Performance in the Developing Rat, Eur. J. Physiol., 1997, vol. 434, pp. 438–444.

    Article  CAS  Google Scholar 

  24. Hseu, S.S., Yien, H.W., Du, F., and Sun, L.S., Heart Rate Variability in Neonatal Rat after Perinatal Cocaine Exposure, Neurotoxicol. Teratol., 1998, vol. 20, pp. 601–605.

    Article  CAS  PubMed  Google Scholar 

  25. Udel’nov, M.S., Fiziologiya serdtsa (Heart Physiology), Moscow, 1975.

  26. Fedorov, V.S., Efficiency of Mono-and Bis-Quarter Substances Disturbing Nerve-Muscle Transmission in Newborn and Adult Rats and Mice, Zh. Evol. Biokhim. Fiziol., 1968, vol. 4, pp. 236–242.

    Google Scholar 

  27. Fisher, R.S., On Characteristics of Cholinergic Structures of the Phrenicodiaphragmal Preparation of Rats of Different Age, Vseros. Symposium “Fiziologicheskaya rol’mediatorov” (All-Russia Symposium “Physiological Role of Transmitters”), Kazan, 1972, pp. 240–241.

  28. Frol’kis, V.V., Processes of Self-Regulation in Ontogenesis, Vedushchie problemy vozrastnoi fiziologii i biokhimii (Leading Problems of Age Physiology and Biochemistry), Moscow, 1966, pp. 247–278.

  29. Kusnetsov, S.V., Reproduction of the Primary Rhythms of Excitation in the Cardiac Activity of Newborn Rat Pups, Byull. Exper. Biol. Med., 1994, no. 4, pp. 422–424.

  30. Kusnetsov, S.V., Paradoxical Cardiac Rhythm in Rat Pups as a Possible Analog of the Syndrome of the Sinus Node Deficiency, Zh. Evol. Biokhim. Fiziol., 2002, vol. 38, pp. 354–364.

    PubMed  Google Scholar 

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Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 2, 2005, pp. 160–167.

Original Russian Text Copyright © 2005 by Kuznetsov, Goncharov, Glashkina.

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Kuznetsov, S.V., Goncharov, N.V. & Glashkina, L.M. Change of Parameters of Functioning of the Cardiovascular and Respiratory Systems in Rats of Different Ages under Effects of Low Doses of the Cholinesterase Inhibitor Phosphacol. J Evol Biochem Phys 41, 201–210 (2005). https://doi.org/10.1007/s10893-005-0055-x

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  • DOI: https://doi.org/10.1007/s10893-005-0055-x

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