INFLUENCE OF NITRIC OXIDE SPATIO TEMPORAL CONCENTRATION GRADIENTS ON CONDITIONS OF HYPOXIA DEVELOPMENT IN TISSUES

DOI: https://doi.org/None

Ya.R. Nartsissov (1,2), S.E. Boronovskiy (1), V.S. Kopylova (1), E.V. Mashkovtseva (1,2) 1 -Institute of cytochemistry and molecular pharmacology, 6th-Radial’naya str., 24/14, Moscow, 115404, Russian Federation 2 -National Research Nuclear University «Moscow Engineering Physics Institute», Kashirskoe Shosse, 31, Moscow, 115409, Russian Federation

Introduction. Nitric oxide is a well-known regulator of different metabolic processes in cells and tissues. Its effect is usually represented as a balanced combination of both mediator and toxic action and the mutual ranges of them are not simply identified. It was previously supposed that inhibition of mitochondrial respiratory chain activity may lead to increase of oxygenated tissue area. The aim of this work is to analyze the mutual influence of spatiotemporal distributions of nitric oxide and oxygen concentrations near the blood vessels. Methods. Estimations of non-steady state gradients of nitric oxide and oxygen were carried out in virtual digital phantoms of rat pial membrane using analytical solutions of the boundary problems for 3D diffusion equation. Results. It was shown that even rapid (100 sec) low amplitude (less than 4,5 nM) nitric oxide gradient forming yields essential increase (more than 2,5 times) of oxygenated area. Conclusion. The observed effect can be considered as an additional compensatory mechanism under early stages of hypoxia and a prohypoxic player under later ones.
Keywords: 
nonsteady-state gradients, nitric oxide, hypoxia, diffusion

Список литературы: 
  1. Seraya I.P., Narcissov Ya.R. Sovremennye predstavleniya o biologicheskoy roli oksida azota. Uspehi sovr. biol. 2002; 122 (3): 249–58.[Seraja I.P., Nartsissov Ya.R. Sovremennye predstavlenija o biologicheskoj roli oksida azota. Uspehi sovr. biol. 2002; 122 (3): 249–58 (in Russian)]
  2. Szydlowska K., Tymianski M. Calcium, ischemia and excitotoxicity. Cell Calcium. 2010; 47 (2): 122–9.
  3. Manoury B., Montiel V., Balligand, J.-L. Nitric oxide synthase in post-ischaemicremodelling: New pathways and mechanisms. Cardiovascular Research. 2012; 94 (2): 304–15.
  4. Iwakiri Y., Kim M.Y. Nitric oxide in liver diseases. Trends in Pharmacological Sciences. 2015; 36 (8), art. no. 1236: 524–36.
  5. Brunori M., Forte E., Arese M., Mastronicola D., Giuffrè A., Sarti P. Nitric oxide and the respiratory enzyme. Biochimica et BiophysicaActa – Bioenergetics. 2006; 1757 (9–10): 1144–54.
  6. Moncada S., Erusalimsky J.D. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nature Reviews Molecular Cell Biology. 2002; 3 (3): 214–20.
  7. Sarti P., Forte E., Giuffrè A., Mastronicola D., Magnifico M.C., Arese M. The chemical interplay between nitric oxide and mitochondrial cytochrome c oxidase: Reactions, effectors and pathophysiology. International J. of Cell Biology. 2012; art. no. 571067.
  8. Palacios-Callender M., Hollis V., Frakich N., Mateo J., Moncada S. Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide. J. of Cell Science. 2007; 120 (1): 160–5.
  9. Hall C.N., Attwell D. Assessing the physiological concentration and targets of nitric oxide in brain tissue. J. of Physiology. 2008; 586 (15): 3597–615.
  10. Thomas D.D., Liu X., Kantrow S.P., and Lancaster J.R., Jr. The biological lifetime of nitric oxide: implications for theperivascular dynamics of NO and O2. Proc. Natl. Acad. Sci. USA. 2001; 98: 355–60.
  11. Cooper C.E. Competitive, Reversible, Physiological? Inhibition of Mitochondrial Cytochrome Oxidase by Nitric Oxide. IUBMB Life. 2003; 55 (10–11): 591–7.
  12. Narcissov Ya.R., Tyukina E.S., Boronovskiy S.E, Sheshegova E.V. Modelirovanie prostranstvenno-vremennyh raspredeleniy koncentraciy metabolitov v fantomah biologicheskih ob``ektov na primere pial`nyh obolochek golovnogo mozga krys. Biofizika. 2013; 58 (5): 887–96.[Nartsissov Ya.R., Tyukina E.S., Boronovsky S.E., Sheshegova E.V. Computer modeling of spatial-time distribution of metabolite concentrations in phantoms of biological objects by example of rat brain pial. Biophysics. 2013; 58 (5): 703–11 (in Russian)]
  13. Seraya I.P., Narcissov Ya.R., Braun G. Matematicheskoe modelirovanie nestacionarnyh prostranstvennyh gradientov oksida azota v myshechnoy stenke krovenosnyh sosudov. Biofizika. 2003; 48 (1): 91–6.[Seraya I.P., Nartsissov Ya.R., Brown G.C. Mathematical modeling of nonstationary spatial nitric oxide gradients in vascular smooth muscle. Biophysics. 2003; 48 (1): 82–6 (in Russian)]
  14. Ganfield R.A., Nair P. & Whalen W.J. Mass transfer,storage, and utilization of O2 in cat cerebral cortex. Am. J. Physiol. 1970; 219: 814–21.
  15. Lowenstein C.J. & Padalko E. iNOS (NOS2) at a glance. J. Cell. Sci. 2004; 117: 2865–7.
  16. Narcissov Ya.R. Boronovskiy S.E., Mashkovceva E.V. Vliyanie geometrii vetvleniya sosudov na uroven` troficheskih narusheniy pri formirovanii ochaga ishemii. Doctor.ru. Nevrologiya i Psihiatriya. 2015; 5 (106): 18–20.[Nartsissov Ya.R., Boronovskij S.E., Mashkovceva E.V. Vlijanie geometrii vetvlenija sosudov na uroven’ troficheskih narushenij pri formirovanii ochaga ishemii. Doctor.ru Nevrologija i Psihiatrija. 2015; 5 (106): 18–20 (in Russian)]