Tags

Type your tag names separated by a space and hit enter

Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.
Int J Mol Sci. 2015 Nov 12; 16(11):27015-31.IJ

Abstract

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

Authors+Show Affiliations

Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-Yang District, Beijing 100020, China. wangguoxing@ccmu.edu.cn. Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, 95# Yong'an Road, Xicheng District, Beijing 100050, China. wangguoxing@ccmu.edu.cn.Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-Yang District, Beijing 100020, China. zqian604@163.com.Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-Yang District, Beijing 100020, China. 2000ywei@sina.com.Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-Yang District, Beijing 100020, China. wu007838@sina.com.Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-Yang District, Beijing 100020, China. lichunsheng@ccmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26569234

Citation

Wang, Guoxing, et al. "Sildenafil Protects Against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System." International Journal of Molecular Sciences, vol. 16, no. 11, 2015, pp. 27015-31.
Wang G, Zhang Q, Yuan W, et al. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System. Int J Mol Sci. 2015;16(11):27015-31.
Wang, G., Zhang, Q., Yuan, W., Wu, J., & Li, C. (2015). Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System. International Journal of Molecular Sciences, 16(11), 27015-31. https://doi.org/10.3390/ijms161126010
Wang G, et al. Sildenafil Protects Against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System. Int J Mol Sci. 2015 Nov 12;16(11):27015-31. PubMed PMID: 26569234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System. AU - Wang,Guoxing, AU - Zhang,Qian, AU - Yuan,Wei, AU - Wu,Junyuan, AU - Li,Chunsheng, Y1 - 2015/11/12/ PY - 2015/08/22/received PY - 2015/10/13/revised PY - 2015/11/03/accepted PY - 2015/11/17/entrez PY - 2015/11/17/pubmed PY - 2016/8/25/medline KW - Ang (1–7) KW - myocardial ischemia KW - porcine model KW - renin-angiotensin system KW - sildenafil SP - 27015 EP - 31 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 16 IS - 11 N2 - Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/26569234/Sildenafil_Protects_against_Myocardial_Ischemia_Reperfusion_Injury_Following_Cardiac_Arrest_in_a_Porcine_Model:_Possible_Role_of_the_Renin_Angiotensin_System_ L2 - https://www.mdpi.com/resolver?pii=ijms161126010 DB - PRIME DP - Unbound Medicine ER -