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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. 2015; 61(3): 3-10


NOS UNCOUPLING IS ACCOMPANIED WITH INDUCTION OF THE OXIDATIVE STRESS AND THE CARDIOHEMODYNAMICS DISTURBANCES IN HYPERTENSION

A.V.Kotsuruba, N.A.Dorofeyeva, V.F.Sagach

    О.О. Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz61.03.003


Abstract

We compared the performance of cardiaohemodynamics and indicators of oxidative and nitrosative stress in the heart and aorta in normotensive Wistar rats (WKR) and spontaneously hypertensive rats (SHR). On the basis of experimentally determined parameters to calculate сNOS uncoupling index and biochemical index of function (BIF) in these organs of the cardiovascular system. In the heart, and especially in the aorta of SHR develop a combined oxidative and nitrosative stress that leads to сNOS uncoupling, BIF lowering that correlate with lowering of systolic and diastolic functions, inhibition of the efficiency Frank-Starling mechanism, oxygen consumption of the heart and increasing arterial stiffness. We made the assumption of the existence of the vicious circle of enhancing oxidative stress in organs of the cardiovascular system due to additional superoxide generation by uncoupling сNOS.

Keywords: heart; aorta; uncoupling cNOS; hypertension; oxidative stress

References

  1. Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflugers Arch. 2010;459(6):923-39. CrossRef PubMed
  2.  
  3. Förstermann U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med. 2008;5(6):338-49. CrossRef PubMed
  4.  
  5. Escobales N, Crespo MJ. Oxidative-nitrosative stress in hypertension. Curr Vasc Pharmacol. 2005;3(3):231-46. CrossRef PubMed
  6.  
  7. Schulz E1, Jansen T, Wenzel P, Daiber A, Münzel T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal. 2008;10(6):1115-26. CrossRef PubMed
  8.  
  9. Thomas SR, Chen K, Keaney JF Jr. Oxidative stress and endothelial nitric oxide bioactivity. Antioxid Redox Signal. 2003;5(2):181-94. CrossRef PubMed
  10.  
  11. Schulz E, Jansen T, Wenzel P, Daiber A, Münzel T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal. 2008;10(6):1115-26. CrossRef PubMed
  12.  
  13. Oliveira-Paula GH, Lacchini R, Tanus-Santos JE. Іnducible nitric oxide synthase as a possible target in hypertension. Curr Drug Targets. 2014;15(2):164-74. CrossRef PubMed
  14.  
  15. Shumilova TE, Nozdrachev AD, Fedorova MA. Role of inorganic nitrite and nitric oxide in the function of cardiovascular system. Ross Fiziol Zh Im I M Sechenova. 2014 ;100(3):301-17 [Russian].
  16.  
  17. Pellegrino D, Parisella ML. Nitrite as a physiological source of nitric oxide and a signalling molecule in the regulation of the cardiovascular system in both mammalian and non-mammalian vertebrates. Recent Pat Cardiovasc Drug Discov. 2010;5(2):91-6. CrossRef PubMed
  18.  
  19. Jansson EA, Huang L, Malkey R, Govoni M, Nihlén C, et all. A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nat Chem Biol. 2008 ;4(7):411-7 CrossRef PubMed
  20.  
  21. Mitchell BM, Cook LG, Danchuk S, Puschett JB. Uncoupled endothelial nitric oxide synthase and oxidative stress in a rat model of pregnancy-induced hypertension. Am J Hypertens. 2007;20(12):1297-304. CrossRef PubMed
  22.  
  23. Chen CA, Lin CH, Druhan LJ, Wang TY, Chen YR, Zweier JL. Superoxide induces endothelial nitric-oxide synthase protein thiyl radical formation, a novel mechanism regulating eNOS function and coupling. JBiol Chem.2011;286:29098–107. CrossRef PubMed PubMedCentral
  24.  
  25. Crabtree MJ, Brixey R, Batchelor H, Hale AB, Channon KM. Integrated redox sensor and effector functions for tetrahydrobiopterin- and glutathionylationdependent endothelial nitric-oxide synthase uncoupling. J Biol Chem. 2013;288:561–9. CrossRef PubMed PubMedCentral
  26.  
  27. Roe ND, Ren J. Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular diseases. Vascul Pharmacol. 2012;57(5):168–72.
  28.  
  29. Karbach S, Wenzel P, Waisman A, Munzel T, Daiber A. eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation. Curr Pharm Des. 2014;20(22):3579-94. CrossRef PubMed
  30.  
  31. Dikalov S, Ungvari Z. Role of mitochondrial oxidative stress in hypertension. Am J Physiol Heart Circ Physiol. 2013;305(10):H1417-27.
  32.  
  33. Konior A, Schramm A, Czesnikiewicz-Guzik M, Guzik TJ. NADPH oxidases in vascular pathology. Antioxid Redox Signal. 2014;20(17):2794-814. CrossRef PubMed PubMedCentral
  34.  
  35. Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care. 2008;31 Suppl 2:S170-80.
  36.  
  37. Cave AC, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, et all. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal. 2006;8(5-6):691-728.
  38.  
  39. Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004;555(Pt 3):589-606.
  40.  
  41. Hernanz R, Briones AM, Salaices M, Alonso MJ. New roles for old pathways? A circuitous relationship between reactive oxygen species and cyclo-oxygenase in hypertension. Clin Sci (Lond). 2014;126(2):111-21. CrossRef PubMed
  42.  
  43. Pacher P., T.Nagayama, P. Mukhopadhyay , S.Batkai , D. A. Kass Measurement of cardiac function using pressurevolume conductance catheter technique in mice and rats. Nat. Protoc:2008,3, № 9:1422–1434.
  44.  
  45. Sharipov RR, Kotsiuruba AV, Kop'iak BS, Sahach VF. Induction of oxidative stress in heart mitochondria in brain focal ischemia-reperfusion and protective effect of ecdysterone. Fiziol Zh. 2014; 60(3):11-7. (Ukrainian).
  46.  
  47. Sharipov RR, Kotsiuruba AV, Kop'iak BS, Sahach VF. Induction of nitrosative stress in mitochondria of rats hearts in experimental ischemia-reperfusion of the brain and its correction by ecdysterone. Fiziol Zh. 2014; 60(5):3-13. (Ukrainian).
  48.  
  49. Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res. 2006 ;71(2):247-58. CrossRef PubMed

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