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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. 2014; 60(4): 3-10


Propargylglycine restores endothelium-dependent relaxation of aortic smooth muscles in old rats

Drachuk KO, Kotsiuruba AV, Baziliuk OV, Stepanenko LH, Sahach VF.

    O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz60.04.003

Abstract

In the study we investigated the effect of blockade сystathionine- ? -lyase (CSE), an enzyme of hydrogen sulfide (H2S) (de novo) synthesis on the endothelium-dependent relaxation of aortic smooth muscle (SM) in old rats. It has been shown that an inhibition of CSE by propargylglycine (PAG) results in restoration of a decreased ACh-induced relaxation of aorta in old rats. This effect of PAG was removed by blocking nitric oxide (NO) synthesis in the endothelial cells. Age-related changes in the levels of H2S, NO2 - and enzyme activity of the constitutive synthesis of NO (cNOS) in the heart, were determined. It has been shown that PAG introduction elevates a decreased levels of H2S, NO2 - and stimulates the suppressed activity of cNOS in old rats. These results suggest that PAG activates alternative ways of H2S synthesis and stimulates the constitutive synthesis of NO. These actions of PAG restore endothelial function in old rats.

Keywords: propargylglycine, hydrogen sulfide, cystathionine-г-lyase, acetylcholine, nitrogen oxide, endothelium, smoothmuscle, aorta, aging, oxidative stress.

References

  1. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease. Circulation. 2003; 107(2):346-54. CrossRef  
  2. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE et al. Population-based study of eventrate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet. 2005; 366(9499):1773-83. CrossRef  
  3. Li H, Forstermann U. Nitric oxide in the pathogenesis of vascular disease. J Pathol. 2000; 190(3): 244-54. CrossRef  
  4. Kojda G. Mechanisms of inotropic effects induced by nitric oxide. Ital Heart J. 2001; 2 Suppl 3:48S-49S. PubMed
  5.  
  6. Sagach VF, Bazilyuk OV, Stepanenko LG, Korcach JuP, Kotsuruba AV. Ace inhibitor enalapril action on nitric oxide synthesis, oxidative metabolism and vascular tone of aging rat. Fiziol Zh. 2007; 53(4):15-26.
  7.  
  8. Cernadas MR, Sanchez de Miguel L, Garcia-Duran M, Gonzalez-Fernandez F, Millas I, Monton M et al. Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circ Res. 1998;83(3):279-86. CrossRef PubMed
  9.  
  10. Lavu M, Bhushan S, Lefer DJ. Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential. Clin Sci (Lond). 2011; 120(6):219-29. CrossRef PubMed
  11.  
  12. Predmore BL, Lefer DJ, Gojon G. Hydrogen Sulfide in Biochemistry and Medicine. Antiox Redox Signal. 2012; 17(1):119-40. CrossRef PubMed PubMedCentral
  13.  
  14. Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci U S A. 2007; 104(39):15560-5. CrossRef PubMed PubMedCentral
  15.  
  16. Calvert JW. Elston M. Nicholson CK. Gundewar S. Jha S. Elrod JW, et al. Genetic and pharmacologic hydrogen sulfide therapy attenuates ischemia-induced heart failure in mice. Circulation. 2010; 122:11–19. CrossRef PubMed PubMedCentral
  17.  
  18. Kazuhisa Kondo, Shashi Bhushan, Adrienne L. King, Sumanth D. Prabhu, Tariq Hamid, Steven Koenig et al. H2S Protects Against Pressure Overload Induced Heart Failure via Upregulation of Endothelial Nitric Oxide Synthase (eNOS). Circulation. 2013; 127(10):1116–1127. CrossRef PubMed PubMedCentral
  19.  
  20. Kondo K, Bhushan S, King AL, Prabhu SD, Hamid T, Koenig S et al. H2S protects against pressure overloadinduced heart failure via upregulation of endothelial nitric oxide synthase. Circulation. 2013; 127:1116–1127. CrossRef PubMed PubMedCentral
  21.  
  22. Kubo S, Kurokawa Y, Doe I, Masuko T, Sekiguchi F, Kawabata A. Hydrogen sul.de inhibits activity of three isoforms of recombinant nitric oxide synthase. Toxicology 2007; 241:92–97. CrossRef PubMed
  23.  
  24. Svenson A.A rapid and sensitive spectrophotometric method for determination of hydrogen sulfide with 2,2'-dipyridyl disulfide. Anal Biochem. 1980; 107:51-55. CrossRef  
  25. Boyde JR, Rahmotullah M. Optimization of conditions for the colorimetric determination of citrulline, using diacetil monoxime. Anal Biochem. 1980; 107:424-431. CrossRef  
  26. Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species and changes in activity of Ca2+- dependent and Ca2+-independent nitric oxide syntases. FEBS Lett. 1991; 1:145-149. CrossRef  
  27. Chin SY, Pandey KN, Shi SJ et al. Increased activity and expression of Ca2+-dependent NOS in renal cortex of ANG II-infused hypertensive rats. Amer J Physiol. 1999; 5:797-804. CrossRef  
  28. Tkachenko MN, Sagach VF, Kotsjuruba AV, Baziljuk OV, Buchanevich AM, Meged EF et al. Endotheliumdependent contractile reactions of vascular smooth muscles and content of free radicals of oxygen of rats in aging. Fiziol Zh. 2002; 48(4):3-13.
  29.  
  30. Moibenko OO, Sahach VF, Shapoval LM, Soloviov AI, Baziliuk OV, Zhukova AV et al. The role of the endothelium and of biologically active substances of endothelial origin in regulating blood circulation and cardiac activity. Fiziol Zh. 1997; 43(1):3-18. PubMed
  31.  
  32. Sagach VF, Baziljuk OV, Kotsjuruba AV, Buchanevich AM. Disturbance of endothelium-dependent vascular responses, arginase and no-synthase pathways of l-arginine metabolism at spontaneously hypertensive rats. Fiziol Zh. 2000;46(3):3-13.
  33.  
  34. Fleenor BS, Seals DR, Zigler ML, Sindler AL. Superoxide- lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice. Aging Cell. 2012; 11:269–276. CrossRef PubMed PubMedCentral
  35.  
  36. Rodriguez-Manas L, El-Assar M, Vallejo S, Lopez-Doriga P, Solis J, Petidier R et al. Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell. 2009;8:226–238. CrossRef PubMed
  37.  
  38. Mayhan WG, Arrick DM, Sharpe GM, Sun H. Age-related alterations in reactivity of cerebral arterioles: role of oxidative stress. Microcirculation. 2008; 15:225–236. CrossRef PubMed
  39.  
  40. Didion SP, Kinzenbaw DA, Schrader LI, Faraci FM. Heterozygous CuZn superoxide dismutase deficiency produces a vascular phenotype with aging. Hypertension. 2006; 48:1072–1079. CrossRef PubMed
  41.  
  42. Yang Y-M, Huang A, Kaley G, Sun D. eNOS uncoupling and endothelial dysfunction in aged vessels. American Journal of Physiology – Heart and Circulatory Physiol. 2009; 297:H1829–H1836. CrossRef PubMed PubMedCentral
  43.  
  44. Donato AJ, Eskurza I, Silver AE, Levy AS, Pierce GL, Gates PE, et al. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ Res. 2007; 100:1659–1666. CrossRef PubMed
  45.  
  46. Whiteman M, Armstrong JS, Chu SH, Jia-Ling S, Wong BS, Cheung NS et al. The novel neuromodulator hydrogen sul?de: An endogenous peroxynitrite scavenger'? J Neurochem. 2004; 90: 765–768. CrossRef PubMed
  47.  
  48. Yan SK, Chang T, Wang H, Wu L, Wang R, Meng QH. Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells. Biochem Biophys Res Commun. 2006; 351:485–491. CrossRef PubMed
  49.  
  50. Lu M, Hu LF, Hu G, Bian JS. Hydrogen sulfide protects astrocytes against H(2)O(2)-induced neural injury via enhancing glutamate uptake. Free Radic Biol Med. 2008; 45:1705–1713. CrossRef PubMed
  51.  
  52. Muzaffar S, Shukla N, Bond M, Newby AC, Angelini GD, Sparatore A et al. Exogenous hydrogen sulfide inhibits superoxide formation, NOX-1 expression and Rac1 activity in human vascular smooth muscle cells. J Vasc Res. 2008; 45:521–528. CrossRef PubMed
  53.  
  54. Wray DW, Nishiyama SK, Harris RA, Zhao J, McDaniel J, Fjeldstad AS et al. Acute reversal of endothelial dysfunction in the elderly after antioxidant consumption. Hypertension. 2012; 59:818–824. CrossRef PubMed PubMedCentral
  55.  
  56. Benetti LR, Campos D, Gurgueira SA, Vercesi AE, Guedes CE, Santos KL et al. Hydrogen sulfide inhibits oxidative stress in lungs from allergic mice in vivo. Eur J Pharmacol. 2013; 698:463–469. CrossRef PubMed
  57.  
  58. King AL, Polhemus DJ, Bhushan S, Otsuka H, Kondo K, Nicholson CK et al. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. Proc Natl Acad Sci. 2014;111(8):3182-7. CrossRef PubMed PubMedCentral

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