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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2005; 51(3): 42-51

Inhibition of nitric oxide synthesisduring bacterial shock in rodents doesnot prevent development of resistant(decompensated) hypotension and death

A.S. Khromov, I.V.Ivanova, A.V. Stefanov

    Institute of Pharmacology and Toxicology, Academy ofMedical Sciences of Ukraine, Kyiv



Abstract

The study subject was the white rat-males Wistar after intra- peritoneal injection of the mixture of St. aureus and B. pyocyaneus daily cultures in the dose calculated as 1 milliard microbial organisms of each species per 100 g b.w., as well as the vascular preparations isolated from aortas of those rats. The aim is to study nitric oxide role in the development of resistant hypotension under generalization of the purulent infection. Infection of the animals with a mixture of gram- positive and gram-negative cultures led to the development of the pathological process, which can be considered as a septic (bacterial) shock. A primary lowering of the vascular tone caused by depression of the myocardial pump and contractile functions was observed. Injection of methylene blue or NOS blockers (L-NAME, S-methyl-thiourea) to the infected animals in the moment of hypotension development caused only a short-term rise in blood pressure. Survival rate in such animals was significantly lower compared to the control infected animals. Repeated injections of those agents hastened death of the experimental animals. The experiments in vitro revealed no dilatory effect of acetylcholine with preserved sensitivity of the vascular preparations to adrenomimetics and exogenous nitric oxide in both control infected animals and animals injected with methylene blue or NOS blockers. The data obtained suggested that resistant hypertension in terminal stages of septic shock is nitric oxide-independent.

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References

  1. Брин В.Б., Зонис Б.Я. Физиология системногокровообращения. Формулы и расчеты. – Из-воРостов. ун-та, 1984. – 88 с.
  2. Лакин Г.Ф. Биометрия. – М.: Высш. школа, 1973. – 343 с.
  3. Хромов О.С. Вплив ліпіну на зміни системногокровообігу у спонтанно-гіпертензивних щурів //Ліки. – 2000. – №3–4. – С. 30–36.
  4. Хромов О.С., Соловйов А.І., Стефанов О.В.Моделювання ендотоксичного та септичного шокуу гризунів: Доклінічні дослідження лікарськихзасобів / За ред. О.В. Стефанова. – К.: Авіцена, 2001. –С.503–515.
  5. Avontuur J.A.M., Boomsma F., Van den MeirackerA.H. et al. Endothelin-1 and blood pressure after ofnitric oxide synthesis in human septic shock // Circulat. –1999. – 99. – P.271–275.
  6. Brady A.J. Nitric oxide, myocardial failure and septicshock (Review) // Int. J. Cardiol. – 1995. – 50. – P.269–272.
  7. Cochran J.B., Genovese F., Ogura S. et al. Effect ofnitric oxide donors and nitric oxide synthase inhibitorsin neonatal rat endotoxic shock // Biochem. Pharmacol. –1999. – 58. – P.687–691.
  8. Davies M.G., Fulton G.J. Haden P. Clinical biology ofnitrie oxide // Brit. J. Surg. – 1995. –82. – Р.1598–1610.
  9. 9. Gray G.A., Schott C., Julou-Schaeffer G. et al. Aninvestigation of the effects of inhibitors of the L-arginine pathway on endotoxin-induced vascularhyporeactivity in vivo // Brit. J. Pharmacol. – 1991. –103. – P.1218–1224.
  10. 10. Groeneveld A.B.J., Bronsveld W., Thijs L.G. Hemo-dynamic determinants of mortality in human septicshock// Surgery. – 1986. – 99. – P.140–152.
  11. Keaney J., Puynia J., Francis S. et al. Methylene bluereverses endotoxin induced hypotension // Circulat.Res. – 1994. – 74. – P.1121–1125.
  12. Kilbourne R.G., Gross S.S., Jubran A. et al. NG-Methyl-L-Arginine inhibits tumor necrosis factor-in-duced hypotension: implications for the involvementof nitric oxide // Proc. Natl. Acad. Sci. USA. – 1990. –87. – P.3629–3632.
  13. Kubichek W., Patterson R„ Witsce D. Impedance car-diography as a noninvasive method of monitoringcardial function and other parameters of cardiovasscu-lar system // Ann. N.Y. Acad. Sci. – 1970. – 170. – P.724–732.
  14. Mitaka C., Hirata Y., IchiKawa T. et al. Effect of nitricoxide synthase inhibitor on hemodynamic change andO2 delivery in septic dogs // Amer. J. Physiol. – 1995. –2, №5, Pt.2. – P.H2017–H2023.
  15. Nava E., Salazar F.J. Comparative effects of nitric ox-ide synthesis inhibitor and catecholamine treatment ina rat model of endotoxin shock // Eur. J. Clin. Invest. –1997. – 27. – P.673–679.
  16. Parker J.L., Myers P.R., Zhong I. Inhibition of endot-helium-dependet vasodilatation by Escherichia coliendotoxin // Shock. – 1994. – 2. – P.451–458.
  17. Parrillo J.E. Pathogenesis of cardiovascular dysfunctionin septic shock. – In: Update in intensive care andemergency medicine/ Ed. Vincent J.L. – Berlin–Heidenberg–New York: Springer, 1989. – 8. – P.317–321.
  18. Schoonover L.L., Stewart A.S., Clifton G.D. Hemody-namic and cardiovascular effects of nitric oxide modu-lation in the therapy of septic shock // Pharmaco-therapy. – 2000. – 20, №10. – P. 1184–1197.
  19. 19. Soloviev A., Stefanov А., Tishkin S., Khromov A. Sa-line containing phosphatidylcholine liposomes possessthe ability to restore endothelial function damaged re-sulting from g-irradiation // J. Physiol. Pharmacol. –2002. – 53, №3. – P.74–81.
  20. 20. Szabo C., Cuzzocrea S., Zingarelli B. et al. Endothelialdysfunction in a rat model of endotoxic shock – Importanceof the activation of poly (ADP-ribose) synthase byperoxynitrite // J. Clin. Invest. – 1997. – 100. – P.723–773.
  21. Szabo C., Salzman A.L., Ischiropoulos H. Endotoxin trig-the expression of an inducible isoform of nitric oxidesynthase and the formation of peroxynitrite in the rataorta in vivo // FEBS Lett. – 1995. –363. – P.235–238.
  22. Veragut P., Krayenbuhl H. Estimation and quatificationof myocardial contractility in the closed- chest dogs //Cardiologia. – 1965. – 47. – P.96–112.
  23. Wu C.C., Szabo C., Chen S.J. et al. Activation osoluble guanylyl cyclase by a factor other then nitricoxide or carbon monoxide contributes to the vascularhyporeactivity to vasoconstrictiors agents in the aortaof rats treated with endotoxin // Biochem. and Biophys.Res. Commun. – 1994. – 201. – P.436–442.
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