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Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction
First Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China
School of Medicine, Nankai University, Tianjin 300071, China
Marshall University Joan C. Edward School of medicine, 1600 Medical Center Drive, Huntington, WV 25701, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 19 November 2012; in revised form: 6 January 2013 / Accepted: 21 January 2013 / Published: 28 January 2013
Abstract: In this study, we evaluate the effect of HO-1 upregulation on blood pressure and cardiac function in the new model of infarct spontaneous hypertensive rats (ISHR). Male spontaneous hypertensive rats (SHR) at 13 weeks (n = 40) and age-matched male Wistar (WT) rats (n = 20) were divided into six groups: WT (sham + normal saline (NS)), WT (sham + Co(III) Protoporphyrin IX Chloride (CoPP)), SHR (myocardial infarction (MI) + NS), SHR (MI + CoPP), SHR (MI + CoPP + Tin Mesoporphyrin IX Dichloride (SnMP)), SHR (sham + NS); CoPP 4.5 mg/kg, SnMP 15 mg/kg, for six weeks, one/week, i.p., n = 10/group. At the sixth week, echocardiography (UCG) and hemodynamics were performed. Then, blood samples and heart tissue were collected. Copp treatment in the SHR (MI + CoPP) group lowered blood pressure, decreased infarcted area, restored cardiac function (left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), +dp/dtmax, (−dp/dtmax)/left ventricular systolic pressure (LVSP)), inhibited cardiac hypertrophy and ventricular enlargement (downregulating left ventricular end-systolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and heart weight/body weight (HW/BW)), lowered serum CRP, IL-6 and Glu levels and increased serum TB, NO and PGI2 levels. Western blot and immunohistochemistry showed that HO-1 expression was elevated in the SHR (MI + CoPP) group, while co-administration with SnMP suppressed the benefit functions mentioned above. In conclusion, HO-1 upregulation can lower blood pressure and improve post-infarct cardiac function in the ISHR model. These functions may be involved in the inhibition of inflammation and the ventricular remodeling process and in the amelioration of glucose metabolism and endothelial dysfunction.
Keywords: hypertension; myocardial infarction; heme oxygenase; bilirubin
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MDPI and ACS Style
Chen, T.-M.; Li, J.; Liu, L.; Fan, L.; Li, X.-Y.; Wang, Y.-T.; Abraham, N.G.; Cao, J. Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction. Int. J. Mol. Sci. 2013, 14, 2684-2706.
Chen T-M, Li J, Liu L, Fan L, Li X-Y, Wang Y-T, Abraham NG, Cao J. Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction. International Journal of Molecular Sciences. 2013; 14(2):2684-2706.
Chen, Tian-meng; Li, Jian; Liu, Lin; Fan, Li; Li, Xiao-ying; Wang, Yu-tang; Abraham, Nader G.; Cao, Jian. 2013. "Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction." Int. J. Mol. Sci. 14, no. 2: 2684-2706.