Skip to main content
SpringerLink
Log in

Role of Nitric Oxide Synthase in the Infarct-Limiting Effect of Normobaric Hypoxia

  • Experimental Papers
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

The study was carried out in male Wistar rats. Animals were randomly divided into normoxic control groups and groups exposed to normobaric hypoxia (NH). NH was modeled via 6 consecutive cycles of hypoxia-reoxygenation: normobaric hypoxia (10 min)/reoxygenation (10 min). All animals underwent coronary artery occlusion (45 min) by applying a ligature to the left coronary artery, and reperfusion (2 h) by removing ligature. The following compounds were administered to rats: the non-selective NO-synthase (NOS) inhibitor L-NAME (10 mg/kg i.v.) before NH or 10 min before coronary occlusion; the inducible NOS inhibitor S-methylthiourea (3 mg/kg i.p.) before coronary occlusion; the neuronal NOS inhibitor 7-nitroindazole (50 mg/kg i.v., 10 min) before coronary artery occlusion; a NO donor diethylenetriamine (2 mg/kg i.v. infusion, 5 min) 1 h before coronary artery occlusion. L-NAME and S-methylthiourea completely abolished the infarct-limiting effect of NH. Diethylenetriamine increased cardiac tolerance to ischemia/reperfusion in normoxic control rats. Thus, iNOS plays an important role in the cardioprotective effect of NH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Baxter GF, Ferdinandy P (2001) Delayed preconditioning of myocardium: current perspectives. Basic Res Cardiol 96: 329–344. https://doi.org/10.1007/s003950170041

    Article  CAS  PubMed  Google Scholar 

  2. Tsibulnikov SY, Maslov LN, Naryzhnaya NV, Ma H, Lishmanov YB, Oeltgen PR, Garlid K (2018) Role of protein kinase C, PI3 kinase, tyrosine kinases, NO-synthase, KATP channels and MPT pore in the signaling pathway of the cardioprotective effect of chronic continuous hypoxia. Gen Physiol Biophys 37: 537–547. https://doi.org/10.4149/gpb_2018013

    Article  CAS  PubMed  Google Scholar 

  3. Guo Y, Stein AB, Wu WJ, Zhu X, Tan W, Li Q, Bolli R (2005) Late preconditioning induced by NO donors, adenosine A1 receptor agonists, and δ1-opioid receptor agonists is mediated by iNOS. Am J Physiol Heart Circ Physiol 289: H22517. https://doi.org/10.1152/ajpheart.00341.2005

    Article  CAS  Google Scholar 

  4. Maslov LN, Naryzhnaya NV, Tsibulnikov SYu, Kolar F, Zhang Y, Wang H, Gusakova AM, Lishmanov YuB (2013) Role of endogenous opioid peptides in the infarct size-limiting effect of adaptation to chronic continuous hypoxia. Life Sci 93: 373–379. https://doi.org/10.1016/j.lfs.2013.07.018

    Article  CAS  PubMed  Google Scholar 

  5. Chiari PC, Bienengraeber MW, Weihrauch D, Krolikowski JG, Kersten JR, Warltier DC, Pagel PS (2005) Role of endothelial nitric oxide synthase as a trigger and mediator of isoflurane-induced delayed preconditioning in rabbit myocardium. Anesthesiology 103: 74–83. https://doi.org/10.1097/00000542-200507000-00014

    Article  CAS  PubMed  Google Scholar 

  6. Jiang X, Shi E, Nakajima Y, Sato S (2004) Inducible nitric oxide synthase mediates delayed cardioprotection induced by morphine in vivo: evidence from pharmacologic inhibition and gene-knockout mice. Anesthesiology 101: 82–88. https://doi.org/10.1097/00000542-200407000-00014

    Article  CAS  PubMed  Google Scholar 

  7. Kamkin AG, Kamkina OV, Shim AL, Bilichenko A, Mitrokhin VM, Kazansky VE, Filatova TS, Abramochkin DV, Mladenov MI (2022) The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytes. Physiol Rep 10: e15246. https://doi.org/10.14814/phy2.15246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Richards MA, Simon JN, Ma R, Loonat AA, Crabtree MJ, Paterson DJ, Fahlman RP, Casadei B, Fliegel L, Swietach P (2020) Nitric oxide modulates cardiomyocyte pH control through a biphasic effect on sodium/hydrogen exchanger-1. Cardiovasc Res 116: 1958–1971. https://doi.org/10.1093/cvr/cvz311

    Article  PubMed  Google Scholar 

  9. Thengchaisri N, Hein TW, Ren Y, Kuo L (2021) Activation of coronary arteriolar PKCβ2 impairs endothelial NO-mediated vasodilation: role of JNK/Rho kinase signaling and xanthine oxidase activation. Int J Mol Sci 22: 9763. https://doi.org/10.3390/ijms22189763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tawa M, Nakano K, Yamashita Y, He Q, Masuoka T, Okamura T, Ishibashi T (2021) Alteration of the soluble guanylate cyclase system in coronary arteries of high cholesterol diet-fed rabbits. Pharmacol Res Perspect 9: e00838. https://doi.org/10.1002/prp2.838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li XD, Cheng YT, Yang YJ, Meng XM, Zhao JL, Zhang HT, Wu YJ, You SJ, Wu YL (2012) PKA-mediated eNOS phosphorylation in the protection of ischemic preconditioning against no-reflow. Microvasc Res 84: 44–54. https://doi.org/10.1016/j.mvr.2012.04.002

    Article  CAS  PubMed  Google Scholar 

  12. Frankenreiter S, Groneberg D, Kuret A, Krieg T, Ruth P, Friebe A, Lukowski R (2018) Cardioprotection by ischemic postconditioning and cyclic guanosine monophosphate-elevating agents involves cardiomyocyte nitric oxide-sensitive guanylyl cyclase. Cardiovasc Res 114: 822–829. https://doi.org/10.1093/cvr/cvy039

    Article  CAS  PubMed  Google Scholar 

  13. Hu L, Zhou L, Wu X, Liu C, Fan Y, Li Q (2014) Hypoxic preconditioning protects cardiomyocytes against hypoxia/reoxygenation injury through AMPK/eNOS/PGC-1α signaling pathway. Int J Clin Exp Pathol 7: 7378–7388.

    PubMed  PubMed Central  Google Scholar 

  14. Cuong DV, Kim N, Youm JB, Joo H, Warda M, Lee JW, Park WS, Kim T, Kang S, Kim H, Han J (2006) Nitric oxide-cGMP-protein kinase G signaling pathway induces anoxic preconditioning through activation of ATP-sensitive K+ channels in rat hearts. Am J Physiol Heart Circul Physiol 290: H1808–H1817. https://doi.org/10.1152/ajpheart.00772.2005

    Article  CAS  Google Scholar 

  15. Costa AD, Pierre SV, Cohen MV, Downey JM, Garlid KD (2008) cGMP signalling in pre- and post-conditioning: the role of mitochondria. Cardiovasc Res 77: 344–352. https://doi.org/10.1093/cvr/cvm050

    Article  CAS  PubMed  Google Scholar 

  16. Yu X, Ge L, Niu L, Lian X, Ma H, Pang L (2018) The Dual Role of Inducible Nitric Oxide Synthase in Myocardial Ischemia/Reperfusion Injury: Friend or Foe? Oxid Med Cell Longev 2018: 8364848. https://doi.org/10.1155/2018/8364848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kraehling JR, Sessa WC (2017) Contemporary Approaches to Modulating the Nitric Oxide-cGMP Pathway in Cardiovascular Disease. Circ Res 120: 1174–1182. https://doi.org/10.1161/CIRCRESAHA.117.303776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun J, Murphy E (2010) Protein S-nitrosylation and cardioprotection. Circ Res 106: 285–296. https://doi.org/10.1161/CIRCRESAHA.109.209452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sun J, Aponte AM, Kohr MJ, Tong G, Steenbergen C, Murphy E (2013) Essential role of nitric oxide in acute ischemic preconditioning: S-nitros(yl)ation versus sGC/cGMP/PKG signaling? Free Radic Biol Med 54: 105–112. https://doi.org/10.1016/j.freeradbiomed.2012.09.005

    Article  CAS  PubMed  Google Scholar 

  20. Sun J, Kohr MJ, Nguyen T, Aponte AM, Connelly PS, Esfahani SG, Gucek M, Daniels MP, Steenbergen C, Murphy E (2012) Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins. Antioxid Redox Signal 16: 45–56. https://doi.org/10.1089/ars.2010.3844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Morciano G, Bonora M, Campo G, Aquila G, Rizzo P, Giorgi C, Wieckowski MR, Pinton P (2017) Mechanistic Role of mPTP in Ischemia-Reperfusion Injury. Adv Exp Med Biol 982: 169–189. https://doi.org/10.1007/978-3-319-55330-6_9

    Article  CAS  PubMed  Google Scholar 

  22. Penna C, Angotti C, Pagliaro P (2014) Protein S-nitrosylation in preconditioning and postconditioning. Exp Biol Med (Maywood) 239: 647–662. https://doi.org/10.1177/1535370214522935

Download references

Funding

The study was supported by the Russian Foundation for Basic Research (RFBR) grant no. 21-515-53003. The section concerned with L-NAME was implemented within the state assignment 122020300042-4. The authors are grateful to N.A. Danilchenko for technical assistance. The study was carried out using the equipment of the “Medical Genomics” Center for Collective Use.

Author information

Authors and Affiliations

  1. Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Tomsk, Russia

    L. N. Maslov, N. V. Naryzhnaya, A. S. Sementsov, I. A. Derkachev & S. V. Gusakova

  2. Department of Mountain and Sleep Medicine and Pulmonary Hypertension, National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan

    Akpay Sarybaev

  3. Kyrgyz-Indian Mountain Biomedical Research Center, Bishkek, Kyrgyzstan

    Akpay Sarybaev

Authors
  1. L. N. Maslov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. V. Naryzhnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. S. Sementsov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. A. Derkachev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. V. Gusakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akpay Sarybaev
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and experimental design (L.N.M., N.V.N.); data collection (A.S.S.); manuscript preparation (I.A.D.); selection of literature sources, participation in data discussion (S.V.G., A.S.).

Corresponding author

Correspondence to I. A. Derkachev.

Ethics declarations

CONFLICT OF INTEREST

The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

Additional information

Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 8, pp. 933–939https://doi.org/10.31857/S0869813922080040.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maslov, L.N., Naryzhnaya, N.V., Sementsov, A.S. et al. Role of Nitric Oxide Synthase in the Infarct-Limiting Effect of Normobaric Hypoxia. J Evol Biochem Phys 58, 1174–1179 (2022). https://doi.org/10.1134/S0022093022040202

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093022040202

Keywords:

Search

Navigation