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.
Highlights
Primary hypertension is a major risk factor of cardiovascular diseases, including cardiomyopathy, coronary artery diseases or even heart failure
Based on these available experimental evidences, we postulated that heme oxygenase 1 (HO-1) upregulation in a new model, infarct spontaneous hypertensive rat (ISHR), could bring in a cardioprotective adaption in the way of suppressing elevated blood pressure, ameliorating pathological ventricular remodeling and improving hypertensive post-infarct cardiac function
We demonstrate for the first time that Heme oxygenase (HO)-1 upregulation through Co(III) Protoporphyrin IX Chloride (CoPP) administration in a new model, infarct spontaneous hypertensive rats (ISHR), possesses a cardiovascular protective function that attenuates blood pressure, alleviates pathological left ventricular remodeling and ameliorates post-infarct cardiac function
Summary
Primary hypertension is a major risk factor of cardiovascular diseases, including cardiomyopathy, coronary artery diseases or even heart failure. From the perspective of myocardial infarction, upregulation of HO-1 activity and expression, no matter which kind of method was adopted, were all able to reduce infarct size, suppress ventricular remodeling and ameliorate post-infarct cardiac function, through the mechanisms of anti-apoptosis and anti-inflammation [11,12,13,14,15]. Based on these available experimental evidences, we postulated that HO-1 upregulation in a new model, infarct spontaneous hypertensive rat (ISHR), could bring in a cardioprotective adaption in the way of suppressing elevated blood pressure, ameliorating pathological ventricular remodeling and improving hypertensive post-infarct cardiac function
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