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Kaur K, Singh N, Dhawan RK. Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats. Iran J Basic Med Sci. 2019;22(12):1415-1423doi: 10.22038/IJBMS.2019.14067.
Kaur, K., Singh, N., & Dhawan, R. K. (2019). Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats. Iranian journal of basic medical sciences, 22(12), 1415-1423. https://doi.org/10.22038/IJBMS.2019.14067
Kaur, Kamaldeep, et al. "Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats." Iranian journal of basic medical sciences vol. 22,12 (2019): 1415-1423. doi: https://doi.org/10.22038/IJBMS.2019.14067
Kaur K, Singh N, Dhawan RK. Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats. Iran J Basic Med Sci. 2019 Dec;22(12):1415-1423. doi: 10.22038/IJBMS.2019.14067. PMID: 32133059; PMCID: PMC7043882.
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Iran J Basic Med Sci. 2019 Dec;22(12):1415-1423. doi: 10.22038/IJBMS.2019.14067.

Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats.

Iranian journal of basic medical sciences

Kamaldeep Kaur, Nirmal Singh, R K Dhawan

Affiliations

  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala.
  2. Department of Pharmacology, Khalsa College of Pharmacy, Amritsar.

PMID: 32133059 PMCID: PMC7043882 DOI: 10.22038/IJBMS.2019.14067

Abstract

OBJECTIVES: Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism of ischaemic postconditioning.

MATERIALS AND METHODS: Isolated rat hearts were subjected to myocardial ischaemia for 30 min followed by reperfusion for 2 hours in control group. Myocardial injury was assessed by measurement of infarct size, left ventricular developed pressure (LVDP), lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes in coronary effluents. The reperfused hearts were homogenised and tissue concentration of nitrite, ADMA level and DDAH enzyme activity was determined.

RESULTS: A significant increase in infarct size, LDH, CK release in coronary effluents and ADMA level in myocardial tissue was observed in control group. The increase in tissue ADMA coincided with reductions of NO tissue concentrations and DDAH activity. Ischaemic postconditioning significantly attenuated ischaemia-reperfusion induced myocardial injury manifested in the terms of decreased infarct size, LDH, CK, tissue ADMA along with increase in NO levels and DDAH enzyme activity. Pretreatment with L-Homocysteine (300 µM), a competitive inhibitor of DDAH, and L-NG-nitroarginine methyl ester (L-NAME; 100 µM), an inhibitor of eNOS, completely abolished ischaemic postconditioning-induced myocardial protection.

CONCLUSION: Enhancing DDAH activity by postconditioning may be a novel target to reduce ADMA level and increase NO bioavailability to prevent myocardial ischaemia-reperfusion injury.

Keywords: ADMA; DDAH; Myocardial ischaemia-reperfusion injury; Nitric Oxide; Postconditioning

Conflict of interest statement

The authors declare that there are no conflicts of interest.

References

  1. FEBS Lett. 2000 Jul 28;478(1-2):1-3 - PubMed
  2. Acta Histochem. 2010 Sep;112(5):413-23 - PubMed
  3. Indian J Clin Biochem. 2014 Jul;29(3):339-44 - PubMed
  4. Anal Biochem. 1982 Oct;126(1):131-8 - PubMed
  5. Int J Cardiol. 2016 Oct 1;220:146-8 - PubMed
  6. J Cardiol. 2013 Apr;61(4):289-94 - PubMed
  7. Eur Heart J. 2014 Aug 1;35(29):1957-70 - PubMed
  8. JAMA. 2011 Feb 9;305(6):585-91 - PubMed
  9. J Biol Chem. 2007 Jan 12;282(2):879-87 - PubMed
  10. Pharmacol Rep. 2013;65(1):122-33 - PubMed
  11. Am J Cardiol. 2005 Mar 15;95(6):729-33 - PubMed
  12. Arq Bras Cardiol. 2015 Feb;104(2):136-43 - PubMed
  13. PLoS One. 2016 Nov 3;11(11):e0165811 - PubMed
  14. Circulation. 1986 Nov;74(5):1124-36 - PubMed
  15. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2252-60 - PubMed
  16. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13527-32 - PubMed
  17. J Mol Cell Cardiol. 2011 Jun;50(6):940-50 - PubMed
  18. Adv Clin Exp Med. 2012 Jul-Aug;21(4):423-31 - PubMed
  19. Cardiovasc Res. 2007 Jul 15;75(2):417-25 - PubMed
  20. Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H579-88 - PubMed
  21. J Cardiovasc Pharmacol. 2003 Aug;42(2):191-6 - PubMed
  22. Am J Physiol. 1990 Dec;259(6 Pt 2):H1660-6 - PubMed
  23. Am Heart J. 1981 May;101(5):593-600 - PubMed
  24. Circulation. 2002 Aug 20;106(8):987-92 - PubMed
  25. Pharmacol Res. 2000 Jun;41(6):613-27 - PubMed
  26. Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2515-21 - PubMed
  27. J Am Heart Assoc. 2016 Apr 18;5(4):e003327 - PubMed
  28. Ann Thorac Surg. 2003 Dec;76(6):2108 - PubMed
  29. Clin Chim Acta. 1962 Sep;7:597-603 - PubMed
  30. J Biol Chem. 2007 Nov 30;282(48):34684-92 - PubMed
  31. Eur J Pharmacol. 2006 Aug 14;543(1-3):97-107 - PubMed
  32. Circulation. 2001 Nov 20;104(21):2569-75 - PubMed
  33. Circulation. 2018 Mar 20;137(12):e67-e492 - PubMed
  34. Heart. 2010 Nov;96(21):1710-5 - PubMed
  35. Methods Find Exp Clin Pharmacol. 2007 Nov;29(9):593-600 - PubMed
  36. Biol Pharm Bull. 2008 Sep;31(9):1745-8 - PubMed
  37. Thromb J. 2009 May 13;7:5 - PubMed
  38. J Am Coll Cardiol. 2003 Sep 17;42(6):998-1003 - PubMed
  39. N Engl J Med. 2007 Sep 13;357(11):1121-35 - PubMed
  40. J Cardiovasc Pharmacol. 2013 Jun;61(6):482-8 - PubMed
  41. J Am Coll Cardiol. 2005 Jun 7;45(11):1775-80 - PubMed
  42. N Engl J Med. 2015 Sep 10;373(11):1021-31 - PubMed
  43. J Med Lab Technol. 1959 Oct;16:265-72 - PubMed

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