Effects of Heme Oxygenase-1 Upregulation on Blood Pressure and Cardiac Function in an Animal Model of Hypertensive Myocardial Infarction

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.

NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure overload

“…±dp/dt max and ±dp/dt min are much more accurate indices in discussing cardiac systolic and diastolic function. 28,29 In this study, LV systolic pressures were similar between KO and WT mice 4 weeks after AB, being statistically higher than shams. Pressure overload significantly decreased ± dp/dt max and ± dp/dt min in KO mice compared with WT mice (Table 1).…”

The role of Nrf2 in oxidative stress-induced endothelial injuries

“…Nrf2-induced expression of HO-1 has potential hypotensive effects. In spontaneously hypertensive rats, HO-1 expression is up-regulated, which suggests its role in hypertension (Chen et al 2013). It has also been demonstrated that HO-1 is involved in the production of carbon monoxide (CO), a direct vasodilatory factor.…”

Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo

“…Moreover, in vitro, only one kidney cell type was studied, while many different cell types are affected by aldosterone in vivo. In the light of existing reports, the fact that we see a raised activation of Nrf2 in vivo at all is astonishing: In chronic kidney disease, as well as in two hypertension models, the Dahl-sensitive hypertensive rat and the spontaneously hypertensive rat, Nrf2 activity and target gene expression were reduced (6,28,60). Only in hypertension induced by the synthetic steroid deoxycorticosterone acetat, an up-regulation was also observed (18).…”