Increased nitric oxide availability worsens the cardiac performance during early re-perfusion period in adult rats
-
Faten M.A. Diab
Abstract
Objectives
Re-perfusion is the standard therapy for acute myocardial infarction, despite the associated pathologies that may contribute to irreversible myocardial injury. The present study aims to clarify the alterations in cardiac activities in response to experimental cardiac ischemic arrest followed by re-perfusion in isolated hearts perfused with nitric oxide (NO) donor, l-arginine, or NO inhibitor, Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), to shed light on the possible role of NO in the re-perfusion process.
Methods
Hearts isolated from adult Wistar rats were studied on Langendorff preparation under basal conditions and during 30 min re-perfusion following 30 min of total global ischemia. Rats were randomly divided into three groups; control and l-arginine or l-NAME infused heart groups. Cardiac tissue content of malondialdhyde, catalase and nitrite was also measured.
Results
Compared to the control group, both l-arginine and l-NAME infused hearts showed increased basal chronotropy and myocardial flow rate. Following ischemia and during the whole period of re-perfusion, the three groups demonstrated significant deterioration in the inotropic activity and compromised myocardial flow rate. l-arginine infused hearts revealed depressed inotropy and chronotropy, weak systolic and diastolic functions with compromised myocardial flow at early 5 min of re-perfusion, yet with significantly higher myocardial flow rate by the end of re-perfusion.
Conclusions
Reducing NO availability by l-NAME revealed mild impact on the ischemia re-perfusion induced contractile dysfunction, whereas excess NO worsens cardiac performance at the early re-perfusion period.
-
Research funding: None declared.
-
Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: All the experimental procedures were carried out in accordance with Guide for the Care and Use of Laboratory Animals and approved by the Research Ethics Committee (REC), Faculty of Medicine, Ain Shams University (protocol number FMASU 277/2015).
References
1. Mozaffarian, D, Benjamin, EJ, Go, AS, Arnett, DK, Blaha, MJ, Cushman, M, et al.. Heart disease and stroke statistics 2015 update: a report from the American Heart Association. Circulation 2015;131:e29–322. https://doi.org/10.1161/CIR.0000000000000152.Search in Google Scholar PubMed
2. Thygesen, K, Alpert, JS, Jaffe, AS, Simoons, ML, Chaitman, BR, White, HD. Third universal definition of myocardial infarction. Nat Rev Cardiol 2012;9:620–33. https://doi.org/10.1038/nrcardio.2012.122.Search in Google Scholar PubMed
3. Jovanovic, A, Jovanovic, S, Lorenz, E, Terzic, A. Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to chemical hypoxia-reoxygenation injury. Circulation 1998;98:1548–55. https://doi.org/10.1161/01.cir.98.15.1548.Search in Google Scholar PubMed
4. Gerczuk, P, Kloner, R. An update on cardioprotection: a review of the latest adjunctive therapies to limit myocardial infarction size in clinical trials. J Am Coll Cardiol 2012;59:969–78. https://doi.org/10.1016/j.jacc.2011.07.054.Search in Google Scholar PubMed
5. Hausenloy, DJ, Yellon, DM. Targeting myocardial reperfusion injury--The search continues. N Engl J Med 2015;373:1073–5. https://doi.org/10.1056/nejme1509718.Search in Google Scholar PubMed
6. Murad, F. Shattuck Lecture, Nitric oxide and cyclic GMP in cell signaling and drug development. N Engl J Med 2006;355:2003–11. https://doi.org/10.1056/nejmsa063904.Search in Google Scholar
7. Ignarro, L. Nitric oxide: a unique endogenous signaling molecule in vascular biology. Biosci Rep 1999;19:51–71. https://doi.org/10.1023/a:1020150124721.10.1023/A:1020150124721Search in Google Scholar
8. Bryan, NS. Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free Radic Biol Med 2006;41:691–701. https://doi.org/10.1016/j.freeradbiomed.2006.05.019.Search in Google Scholar PubMed
9. Förstermann, U, Sessa, W. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33:829–37. https://doi.org/10.1093/eurheartj/ehr304.Search in Google Scholar PubMed PubMed Central
10. Xia, Y, Dawson, V, Dawson, T, Snyder, S, Zweier, J. Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc Natl Acad Sci USA 1996;93:6770–4. https://doi.org/10.1073/pnas.93.13.6770.Search in Google Scholar PubMed PubMed Central
11. Ayobe, H, Tarazi, R. Beta-adrenoceptors and responsiveness in cardiac hypertrophy associated with renal hypertension in renovascular hypertensive rats. Clin Sci (Lond) 1984;67:51–9. https://doi.org/10.1042/cs0670051.Search in Google Scholar PubMed
12. Kostić, MM, Rosić, GL, Segal, MB, Rosić, MA. Biphasic L-arginine uptake by the isolated Guinea-pig heart. Exp Physiol 1995;80:969–79. https://doi.org/10.1113/expphysiol.1995.sp003908.Search in Google Scholar PubMed
13. Lochner, A, Marais, E, Genade, S, Moolman, JA. Nitric oxide: a trigger for classic preconditioning? Am J Physiol Heart Circ Physiol 2000;279:H2752–65. https://doi.org/10.1152/ajpheart.2000.279.6.h2752.Search in Google Scholar PubMed
14. Satoh, K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978;90:37–43. https://doi.org/10.1016/0009-8981(78)90081-5.Search in Google Scholar PubMed
15. Aebi, H. Catalase in vitro. Methods Enzymol 1984;105:121–6. https://doi.org/10.1016/s0076-6879(84)05016-3.Search in Google Scholar PubMed
16. Montgomery, HAC, Dymock, J. The determination of nitrite in water. Analyst 1961;86:414–6. https://doi.org/10.1039/an9618600748.Search in Google Scholar
17. Behmenburg, F, Dorsch, M, Huhn, R, Mally, D, Heinen, A, Hollmann, M, et al.. Impact of mitochondrial Ca2+ sensitive potassium (mbkca) channels in sildenafil-induced cardioprotection in rats. PLoS One 2015;10: e0144737. https://doi.org/10.1371/journal.pone.0144737.Search in Google Scholar PubMed PubMed Central
18. Hu, M, Zhou, B, Mao, H, Sheng, Q, Du, B, Chen, J, et al.. Exogenous hydrogen sulfide postconditioning protects isolated rat hearts from ischemia reperfusion injury through Sirt1/PGC-1α signaling pathway. Int Heart J 2016;57:477–82. https://doi.org/10.1536/ihj.15-506.Search in Google Scholar PubMed
19. Fellet, A, Boveris, A, Arranz, C, Balaszczuk, A. Cardiac mitochondrial nitric oxide: a regulator of heart rate? Am J Hypertens 2008;21:377–81. https://doi.org/10.1038/ajh.2007.90.Search in Google Scholar PubMed
20. Musialek, P, Lei, M, Brown, H, Paterson, D, Casadei, B. Nitric oxide can increase heart rate by stimulating the hyperpolarization-activated inward current, I (f). Circ Res 1997;81:60–8. https://doi.org/10.1161/01.res.81.1.60.Search in Google Scholar PubMed
21. Salihi, A, Shekha, M, Hamadamin, P, Maulood, I, Rasul, K, Salim, M, et al.. In vivo cardiac electrical activity of nitric oxide in barium chloride treated male rats. AIP Conf Proc 2017;1888:020048.10.1063/1.5004325Search in Google Scholar
22. Fellet, A, Balaszczuk, A, Arranz, C, López-Costa, J, Boveris, A, Bustamante, J. Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases. Am J Physiol Heart Circ Physiol 2006;291:H1246–54. https://doi.org/10.1152/ajpheart.00711.2005.Search in Google Scholar PubMed
23. Navarro, A. Mitochondrial nitric oxide synthase and the regulation of heart rate. Am J Hypertens 2008;21:485. https://doi.org/10.1038/ajh.2008.22.Search in Google Scholar PubMed
24. Ke, Z, Gao, A, Xu, P, Wang, J, Ji, L, Yang, J. Preconditioning with PEP-1-SOD1 fusion protein attenuates ischemia/reperfusion-induced ventricular arrhythmia in isolated rat hearts. Exp Ther Med 2015;10:352–6. https://doi.org/10.3892/etm.2015.2440.Search in Google Scholar PubMed PubMed Central
25. Yuan, X, Niu, H, Wang, P, Lu, J, Zhao, H, Liu, S, et al.. Cardioprotective effect of licochalcone D against myocardial ischemia reperfusion injury in Langendorff-perfused rat hearts. PLoS One 2015;10: e0128375. https://doi.org/10.1371/journal.pone.0128375.Search in Google Scholar PubMed PubMed Central
26. Mahmoudabady, M, Lashkari, M, Niazmand, S, Soukhtanloo, M. Cardioprotective effects of Achillea wilhelmsii on the isolated rat heart in ischemia–reperfusion. J Tradit Complement Med 2017;7:501–7. https://doi.org/10.1016/j.jtcme.2016.12.010.Search in Google Scholar PubMed PubMed Central
27. Heusch, P, Aker, S, Boengler, K, Deindl, E, van de Sand, A, Klein, K, et al.. Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation. Am J Physiol Heart Circ Physiol 2010;299:H446–53. https://doi.org/10.1152/ajpheart.01034.2009.Search in Google Scholar PubMed
28. Soskić, SS, Dobutović, BD, Sudar, EM, Obradović, MM, Nikolić, DM, Djordjevic, JD, et al.. Regulation of inducible Nitric Oxide synthase (iNOS) and its potential role in insulin resistance, diabetes and heart failure. Open Cardiovasc Med J 2011;5:153–63. https://doi.org/10.2174/1874192401105010153.Search in Google Scholar PubMed PubMed Central
29. Heidorn, M, Frodermann, T, Böning, A, Schreckenberg, R, Schlüter, K. Citrulline improves early post-ischemic recovery or rat hearts in vitro by shifting arginine metabolism from polyamine to nitric oxide formation. Clin Med Insights Cardiol 2018;12. 1179546818771908. https://doi.org/10.1177/1179546818771908.Search in Google Scholar PubMed PubMed Central
30. Kawaguchi, H, Shin, S, Wang, Y, Inukai, M, Kato, M, Matsuo-Okai, Y, et al.. In vivo gene transfection of human endothelial cell nitric oxide synthase in cardiomyocytes causes apoptosis-like cell death. Identification using Sendai virus-coated liposomes. Circulation 1997;95:2441–7. https://doi.org/10.1161/01.cir.95.10.2441.Search in Google Scholar PubMed
31. Brown, C, Borutaite, V. Nitric oxide inhibition of mitochondrial respiration and its role in cell death. Free Radic Biol Med 2002;33:1440–50. https://doi.org/10.1016/s0891-5849(02)01112-7.Search in Google Scholar PubMed
32. Smith, JA, Shah, AM, Lewis, MJ. Factors released from endothelium of the ferret and pig modulate myocardial contraction. J Physiol 1991;439:1–14. https://doi.org/10.1113/jphysiol.1991.sp018653.Search in Google Scholar PubMed PubMed Central
33. Paulus, WJ, Shah, AM. NO and cardiac diastolic function. Cardiovasc Res 1999;43:595–606. https://doi.org/10.1016/s0008-6363(99)00151-0.Search in Google Scholar PubMed
34. Yellon, DM, Hausenloy, DJ. Myocardial reperfusion injury. N Engl J Med 2007;357:1121–35. https://doi.org/10.1056/nejmra071667.Search in Google Scholar
35. Ohtani, H, Katoh, H, Tanaka, T, Saotome, M, Urushida, T, Satoh, H, et al.. Effects of nitric oxide on mitochondrial permeability transition pore and thiol-mediated responses in cardiac myocytes. Nitric Oxide 2012;26:95–101. https://doi.org/10.1016/j.niox.2011.12.007.Search in Google Scholar PubMed
36. Zhang, F, Xia, Y, Yan, W, Zhang, H, Zhou, F, Zhao, S, et al.. Sphingosine 1-phosphate signaling contributes to cardiac inflammation, dysfunction, and remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol 2016;310:H250–61. https://doi.org/10.1152/ajpheart.00372.2015.Search in Google Scholar PubMed
37. Ibáñez, B, Heusch, G, Ovize, M, Van de Werf, F. Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 2015;65:1454–71. https://doi.org/10.1016/j.jacc.2015.02.032.Search in Google Scholar PubMed
38. Andelová, E, Barteková, M, Pancza, D, Styk, J, Ravingerová, T. The Role of NO in ischemia/reperfusion injury in isolated rat heart. Gen Physiol Biophys 2005;24:411–26.Search in Google Scholar
39. Morita, M, Hayashi, T, Ochiai, M, Maeda, M, Yamaguchi, T, Ina, K, et al.. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability. Biochem Biophys Res Commun 2014;454:53–7. https://doi.org/10.1016/j.bbrc.2014.10.029.Search in Google Scholar PubMed
40. Dick, G, Tune, J. Role of potassium channels in coronary vasodilation. Exp Biol Med 2010;235:10–22. https://doi.org/10.1258/ebm.2009.009201.Search in Google Scholar PubMed
41. Reffelmann, T, Hale, SL, Li, G, Kloner, R. Relationship between no reflow and infarct size as influenced by the duration of ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2002;282:H766–72. https://doi.org/10.1152/ajpheart.00767.2001.Search in Google Scholar PubMed
42. Goodwill, A, Dick, G, Kiel, A, Tune, J. Regulation of coronary blood flow. Comp Physiol 2017;7:321–82. https://doi.org/10.1002/cphy.c160016.Search in Google Scholar PubMed PubMed Central
43. Colin, P, Ghaleh, B, Monnet, X, Hittinger, L, Berdeaux, A. Effect of graded heart rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs. J Pharmacol Exp Therapeut 2004;308:236–40. https://doi.org/10.1124/jpet.103.059717.Search in Google Scholar PubMed
44. Nishikawa, Y, Ogawa, S. Importance of nitric oxide in the coronary artery at rest and during pacing in humans. J Am Coll Cardiol 1997;29:85–92. https://doi.org/10.1016/s0735-1097(96)00429-9.Search in Google Scholar PubMed
45. Burgoyne, J, Oka, S, Ale-Agha, N, Eaton, P. Hydrogen peroxide sensing and signaling by protein kinases in the cardiovascular system. Antioxidants Redox Signal 2013;18:1042–52. https://doi.org/10.1089/ars.2012.4817.Search in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorials
- Deiodination and tumor progression: the interplay between thyroid hormones intracellular activation and the androgen signal
- The intricate role of glutamine in pathophysiological contexts
- Reviews
- Zebrafish as a model organism – can a fish mimic human?
- Phytocompounds and their molecular targets in immunomodulation: a review
- Original Articles
- Host–parasite relationship modulates the effect of African mistletoe leaves on the cholinergic, monoaminergic and carbohydrate hydrolyzing enzymes in fruit fly
- Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats
- Chronic exposure of industrial grade calcium carbide and ethylene glycol exert genotoxic effect in Wistar albino rats
- A four-year review of uterine rupture at a secondary health facility in Okitipupa, Southwest Nigeria
- Increased nitric oxide availability worsens the cardiac performance during early re-perfusion period in adult rats
- Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers
- Tobacco use and clinical leukoplakia lesions among south Indian tribes
- Carcinogen sodium arsenite disrupts antioxidant and redox homeostasis in Drosophila melanogaster
- No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population
- Cardioprotective effect of Justicia gendarussa on doxorubicin induced toxicity in mice
- Lung ultrasound-guided PEEP titration in COVID–19 patients treated with CPAP
- Short Communication
- Effects of the gaseous signalling molecule nitroxyl (HNO) on myenteric neurons governing intestinal motility
Articles in the same Issue
- Frontmatter
- Editorials
- Deiodination and tumor progression: the interplay between thyroid hormones intracellular activation and the androgen signal
- The intricate role of glutamine in pathophysiological contexts
- Reviews
- Zebrafish as a model organism – can a fish mimic human?
- Phytocompounds and their molecular targets in immunomodulation: a review
- Original Articles
- Host–parasite relationship modulates the effect of African mistletoe leaves on the cholinergic, monoaminergic and carbohydrate hydrolyzing enzymes in fruit fly
- Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats
- Chronic exposure of industrial grade calcium carbide and ethylene glycol exert genotoxic effect in Wistar albino rats
- A four-year review of uterine rupture at a secondary health facility in Okitipupa, Southwest Nigeria
- Increased nitric oxide availability worsens the cardiac performance during early re-perfusion period in adult rats
- Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers
- Tobacco use and clinical leukoplakia lesions among south Indian tribes
- Carcinogen sodium arsenite disrupts antioxidant and redox homeostasis in Drosophila melanogaster
- No association of the common Asian mitochondrial DNA haplogroups with lung cancer in East Indian population
- Cardioprotective effect of Justicia gendarussa on doxorubicin induced toxicity in mice
- Lung ultrasound-guided PEEP titration in COVID–19 patients treated with CPAP
- Short Communication
- Effects of the gaseous signalling molecule nitroxyl (HNO) on myenteric neurons governing intestinal motility