Isoproterenol-mediated heme oxygenase-1 induction inhibits high mobility group box 1 protein release and protects against rat myocardial ischemia/reperfusion injury in vivo

Isoproterenol (ISO) has been reported to inhibit high mobility group box 1 (HMGB1) protein release via heme oxygenase-1 (HO-1) induction in lipopolysaccharide (LPS)-activated RAW 264.7 cells and increase the survival rate of cecal ligation and puncture (CLP)-induced septic mice. Therefore, it was examined whether ISO-mediated HO-1 induction inhibits HMGB1 release in cardiac myocytes and attenuates myocardial ischemia/reperfusion (I/R) injury in rats. Anesthetized male rats were pretreated with ISO [intraperitoneal (i.p.) injection of 10 mg/kg] prior to ischemia in the absence and/or presence of zinc protoporphyrin IX (ZnPPIX, i.p., 10 mg/kg), which is an inhibitor of HO-1, and then subjected to ischemia for 30 min followed by reperfusion for 24 h. The myocardial I/R injury and oxidative stress were assessed. In addition, the HO-1 protein and HMGB1 expression were measured by western blot analysis. ISO significantly attenuated the myocardial I/R injury, reduced oxidative stress, and induced HO-1 and reduced HMGB1 release. However, all these effects caused by ISO were significantly reversed in the presence of ZnPPIX. These results suggested that ISO has a pivotal role in the protective effects on myocardial I/R injury. This protection mechanism is possibly due to the inhibition of HMGB1 release via the induction of HO-1.