The functional significance of this GRmediated transcriptional regulation is further demonstrated by the finding that dexamethasone treatment increased AT1aR mRNA and AT1R protein Delamanid expression and decreased AT2R mRNA and protein expression in the heart. The finding that RU486 inhibited dexamethasone-induced effects on transcriptional regulation and AT1R and AT2R expression in the heart is consistent with the previous finding of the direct effect of RU486 in inhibiting dexamethasone-mediated suppression of AT2R in isolated hearts, supporting the notion of a direct GR-dependent mechanism. Although changes in Ang II levels may contribute to cardiac pathophysiology, recent studies have demonstrated that alteration of Ang II receptor expression without changes in Ang II in stressed hearts plays an important role in regulating cardiac function. While it is not clear whether ischemia/reperfusion increases Ang II expression and/or release locally in the isolated heart in a Langendorff Entrectinib (RXDX-101) preparation in the present study, the findings that dexamethasone treatment significantly increased AT1R abundance in the heart and blockade of AT1R by losartan abrogated dexamethasone-induced protective effect, suggest an important role of increased AT1R expression in the glucocorticoid-mediated cardioprotection. The finding of increased PKCe expression and the active form of p-PKCe in the heart of dexamethasone-treated animals is intriguing and suggests a possible mechanism in the cardioprotection observed. Angiotensin II receptors exert a regulatory effect on PKCe expression and activity. Thus, blockade of AT2R with PD123319 increased PKCe expression and AT1R stimulation and AT2R inhibition mimic ischemic preconditioning by increasing PKCe activity. In the present study, we demonstrated that dexamethasone treatment significantly increased PKCe mRNA and protein expression, as well as increased the active form of pPKCe in the heart in a GR-dependent manner. Whereas whether this GR-induced increase in PKCe expression and activity in the heart was mediated by angiotensin II receptors remains to be determined, that dexamethasone treatment up-regulated PKCe expression and activity has been demonstrated in porcine coronary arteries.