Effect of Nicorandil on Endothelial Markers and Tissue Remodeling in Pulmonary Arterial Hypertension Model of Male Rats

المؤلفون

  • Taha Hashim Ahmed Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq https://orcid.org/0009-0006-4298-9015
  • Bahir Abdul-Razzaq Mshimesh Department of Pharmacology and Toxicology, College of Pharmacy, Mutansiriya University, Baghdad Iraq
  • Israa Burhan Raoof Department of Clinical Lab Sciences, College of Pharmacy, Mustansiriya University, Baghdad, Iraq

DOI:

https://doi.org/10.54133/ajms.v5i1S.334

الكلمات المفتاحية:

Anti-apoptotic effect، Endothelin-1، Nicorandil,، NFκB، Nitric oxide، Pulmonary arterial hypertension

الملخص

Background: Chronic pulmonary arterial hypertension (PAH) is a rare, long-lasting illness that makes pulmonary artery endothelial cells (PAEC) not work properly and leads to heart failure and death. Objective: To evaluate the effect of nicorandil in the treatment of PAH compared to tadalafil in a rat model of monocrotaline-induced PAH. Methods: Monocrotaline injection (60 mg/kg) was used for the induction of PAH in male rats; healthy control and induction groups were not treated. The other 4 groups were treated with either nicorandil or tadalafil with or without treatment blockers (glimepiride and N-Nitroarginine methyl ester (L-NAME)) for 21 days orally. Serum was obtained for assessment of endothelin-1 (ET-1) and tissue harvested for nuclear factor kappa B (NFκB) by ELISA, western blot analysis of endothelial nitric oxide synthase (eNOS), and an apoptosis assay to examine the endothelial function. Results: Nicorandil showed a significant reduction in ET-1 and significant elevation in eNOS compared to the induction group, with comparable efficacy to tadalafil; blocker groups showed significantly elevated levels of ET-1 and reduced levels of eNOS compared to healthy control; NFκB was significantly inhibited in nicorandil and tadalafil groups and significantly elevated in blocker and induction groups; while in the TUNEL apoptosis assay, nicorandil showed the highest level of inhibition to apoptosis with apparently normal endothelium lining. Conclusions: Nicorandil shows anti-inflammatory, antiapoptotic, and enhanced endothelial morphology and function compared to the induction model.

التنزيلات

بيانات التنزيل غير متوفرة بعد.

المراجع

Coons JC, Pogue K, Kolodziej AR, Hirsch GA, George MP. Pulmonary arterial hypertension: a pharmacotherapeutic Update. Curr Cardiol Rep. 2019;21. doi:10.1007/s11886-019-1235-4.

Arnold ND, Pickworth JA, West LE, Dawson S, Carvalho JA, Casbolt H, et al. A therapeutic antibody targeting osteoprotegerin attenuates severe experimental pulmonary arterial hypertension. Nat Commun. 2019;10. doi: 10.1038/s41467-019-13139-9.

Corssac GB, Bonetto JP, Campos-Carraro C, Cechinel LR, Zimmer A, Parmeggiani B, et al. Pulmonary arterial hypertension induces the release of circulating extracellular vesicles with oxidative content and alters redox and mitochondrial homeostasis in the brains of rats. Hyperten Res. 2021;44. doi: 10.1038/s41440-021-00660-y.

Dubroff J, Melendres L, Lin Y, Beene DR, Ketai L. High geographic prevalence of pulmonary artery hypertension: associations with ethnicity, drug use, and altitude. Pulm Circ. 2020;10. doi: 10.1177/2045894019894534.

Raina A, Humbert M. Risk assessment in pulmonary arterial hypertension. Eur Respir Rev. 2016;25. doi: 10.1183/16000617.0077-2016.

Harrison F, Dave M, Abby P, David B. Five-year outcomes of patients enrolled in the registry to evaluate early and long-term pulmonary arterial hypertension (PAH) disease management (REVEAL). Chest. 2015;148:1043–1954. doi: 10.1378/chest.15-0300.

Rajagopal S, Yu YRA. The pathobiology of pulmonary arterial hypertension. Cardiol Clin. 2022;40:1-12. doi: 10.1016/j.ccl.2021.08.001.

Tettey A, Jiang Y, Li X, Li Y. Therapy for pulmonary arterial hypertension: Glance on nitric oxide pathway. Front Pharmacol. 2021;12. doi: 10.3389/fphar.2021.767002.

Taira N. Similarity and dissimilarity in the mode and mechanism of action between nicorandil and classical nitrates: An overview. J Cardiovasc Pharmacol. 1987;10. doi: 10.1097/00005344-198706108-00002.

Zhang M, Zhang H, Liu C, Li X, Ling M, Wang Z, et al. Myocardial protective effects of nicorandil on rats with type 2 diabetic cardiomyopathy. Med Sci Monit Basic Res. 2018;24. doi: 10.12659/MSMBR.910974.

Yap A, Choo Y. Phytochemical studies of Malaysian Crotalaria mucronata. Open Conf Proc J. 2015;4. doi: 10.2174/2210289201304010143.

Oh JG, Ishikawa K. Experimental models of cardiovascular diseases: Overview. Method Mol Biol. 2018;1816. doi: 10.1007/978-1-4939-8597-5_1.

Lenz M, Kaun C, Krychtiuk KA, Haider P, Brekalo M, Maier N, et al. Effects of nicorandil on inflammation, apoptosis and atherosclerotic plaque progression. Biomedicines. 2021;9. doi: 10.3390/biomedicines9020120.

Leong ZP, Hikasa Y. Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats. Vascul Pharmacol. 2019;122-123. doi: 10.1016/j.vph.2019.106599.

Sahara M, Sata M, Morita T, Hirata Y, Nagai R. Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension. PLoS One. 2012;7. doi: 10.1371/journal.pone.0033367.

Dong Y, Chen YT, Yang YX, Shou D, Li CY. Urinary metabolomic profiling in Zucker diabetic fatty rats with type 2 diabetes mellitus treated with glimepiride, metformin, and their combination. Molecules. 2016;21. doi: 10.3390/molecules21111446.

Al-Shawi N, Al-Rakhat I. Effects of hydrochlorothiazide on tenofovir disoproxil fumarate-induced nephrotoxicity in rats. Iraqi J Pharm Sci. 2019;28. doi: 10.31351/vol28iss2pp58-64.

Al-Khfajy W, Arif I, Al-Sudani B. Role of fasting mimicking diet in farnesoid x receptor for suppressing epithelial-to-mesenchymal transition, cell cycle progression, and viability of prostate cancer cells. Iraqi J Pharm Sci. 2023;32. doi: 10.31351/vol32iss1pp115-124.

Maidana DE, Tsoka P, Tian B, Dib B, Matsumoto H, Kataoka K, et al. A novel imagej macro for automated cell death quantitation in the retina. Invest Ophthalmol Vis Sci. 2015;56. doi: 10.1167/iovs.15-17599.

Redel-Traub G, Sampson KJ, Kass RS, Bohnen MS. Potassium channels as therapeutic targets in pulmonary arterial hypertension. Biomolecules. 2022;12:2-16. doi: 10.3390/biom12101341.

Nagendran J, Sutendra G, Paterson I, Champion HC, Webster L, Chiu B, et al. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res. 2013;112. doi: 10.1161/circresaha.111.300448.

Chen Z, Chen X, Li S, Huo X, Fu X, Dong X. Nicorandil improves myocardial function by regulating plasma nitric oxide and endothelin-1 in coronary slow flow. Coron Artery Dis. 2015;26. doi: 10.1097/MCA.0000000000000179.

Zhao JL, Yang YJ, Zhang YH, Pei WD, Sun YH, Zhai M, et al. Intravenous nicorandil preserves endothelial junctions by decreasing endothelin-1 via activation of ATP-sensitive K+ channel. J Vas Dis. 2007;36. doi: 10.1024/0301-1526.36.3.175.

Bourque SL, Davidge ST, Adams MA. The interaction between endothelin-1 and nitric oxide in the vasculature: New perspectives. Am J Physiol Regul Integr Comp Physiol. 2011;300. doi: 10.1152/ajpregu.00397.2010.

Takahashi K, Komaru T, Takeda S, Sato K, Kanatsuka H, Shirato K. Nitric oxide inhibition unmasks ischemic myocardium-derived vasoconstrictor signals activating endothelin type a receptor of coronary microvessels. Am J Physiol Heart Circ Physiol. 2005;289. doi: 10.1152/ajpheart.00667.2004.

Janaszak‐jasiecka A, Siekierzycka A, Płoska A, Dobrucki IT, Kalinowski L. Endothelial dysfunction driven by hypoxia—the influence of oxygen deficiency on no bioavailability. Biomolecules. 2021;11. doi: 10.3390/biom11070982.

Varshney R, Ali Q, Wu C, Sun Z. Monocrotaline-induced pulmonary hypertension involves downregulation of antiaging protein klotho and eNOS activity. Hypertension. 2016;68. doi: 10.1161/hypertensionaha.116.08184.

Lee MY, Tsai KB, Hsu JH, Shin SJ, Wu JR, Yeh JL. Liraglutide prevents and reverses monocrotaline-induced pulmonary arterial hypertension by suppressing ET-1 and enhancing eNOS/sGC/PKG pathways. Sci Rep. 2016;6. doi: 10.1038/srep31788.

Refaie MMM, Shehata S, El-Hussieny M, Abdelraheem WM, Bayoumi AMA. Role of ATP-sensitive potassium channel (KATP) and eNOS in mediating the protective effect of nicorandil in cyclophosphamide-induced cardiotoxicity. Cardiovasc Toxicol. 2020;20. doi: 10.1007/s12012-019-09535-8.

Ghosh S, Gupta M, Xu W, Mavrakis DA, Janocha AJ, Comhair SAA, et al. Phosphorylation inactivation of endothelial nitric oxide synthesis in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2016;310. doi: 10.1152/ajplung.00092.2016.

Vignozzi L, Filippi S, Comeglio P, Cellai I, Morelli A, Sarchielli E, et al. P-01-067 effects of chronic treatment with tadalafil in monocrotaline-induced pulmonary hypertensive rat model. J Sex Med. 2016;13. doi: 10.1016/j.jsxm.2016.03.218.

Serizawa K, Yogo K, Aizawa K, Tashiro Y, Ishizuka N. Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats. Cardiovasc Diabetol. 2011;10:105. doi: 10.1186/1475-2840-10-105.

Price LC, Caramori G, Perros F, Meng C, Gambaryan N, Dorfmuller P, et al. Nuclear factor κ-B is activated in the pulmonary vessels of patients with end-stage idiopathic pulmonary arterial hypertension. PLoS One. 2013;8. doi: 10.1371/journal.pone.0075415.

Zhai C, Shi W, Feng W, Zhu Y, Wang J, Li S, et al. Activation of AMPK prevents monocrotaline-induced pulmonary arterial hypertension by suppression of NF-κB-mediated autophagy activation. Life Sci. 2018;208. doi: 10.1016/j.lfs.2018.07.018.

Chen F, Chen ZQ, Zhong GL, Zhu JJ. Nicorandil inhibits TLR4/MyD88/NF-κB/NLRP3 signaling pathway to reduce pyroptosis in rats with myocardial infarction. Exp Biol Med. 2021;246. doi: 10.1177/15353702211013444.

Yoshiyuki H, Kikuo K, Steven G. Retraction of: NO suppresses while peroxynitrite sustains NF-κB: a paradigm to rationalize cytoprotective and cytotoxic actions attributed to NO. Cardiovasc Res. 2011;92. doi: 10.1093/cvr/cvr223.

Caviedes A, Maturana B, Corvalán K, Engler A, Gordillo F, Varas-Godoy M, et al. eNOS-dependent S-nitrosylation of the NF-κB subunit p65 has neuroprotective effects. Cell Death Dis. 2021;12. doi: 10.1038/s41419-020-03338-4.

Millar MW, Fazal F, Rahman A. Therapeutic targeting of NF-κB in acute lung injury: A double-edged sword. Cells. 2022;11. doi: 10.3390/cells11203317.

Balligand JL, Feron O, Dessy C. eNOS activation by physical forces: From short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev. 2009;89. doi: 10.1152/physrev.00042.2007.

Gopalakrishnan M, Molinari EJ, Shieh CC, Monteggia LM, Roch JM, Whiteaker KL, et al. Pharmacology of human sulphonylurea receptor SUR1 and inward rectifier K+ channel Kir6.2 combination expressed in HEK-293 cells. Br J Pharmacol. 2000;129:1323-1332. doi: 10.1038/sj.bjp.0703181.

Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Jain A, et al. The risk of overall mortality in patients with type 2 diabetes receiving glipizide, glyburide, or glimepiride monotherapy: A retrospective analysis. Diabetes Care. 2010;33:1224-1229. doi: 10.2337/dc10-0017.

Akopova OV. On the impact of K(ATP) channel opening on mitochondrial reactive oxygen species production. Histol Cytol Embryol. 2017;1. doi: 10.15761/hce.1000115.

التنزيلات

منشور

2023-11-04

كيفية الاقتباس

Ahmed, T. H., Mshimesh, B. A.-R., & Raoof, I. B. (2023). Effect of Nicorandil on Endothelial Markers and Tissue Remodeling in Pulmonary Arterial Hypertension Model of Male Rats. Al-Rafidain Journal of Medical Sciences, 5(1S), S87–93. https://doi.org/10.54133/ajms.v5i1S.334

إصدار

القسم

Original article

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