It has been well documented that PKCe plays an important role in ischemic preconditioning and is necessary and sufficient for cardioprotective effects in ischemia-reperfusion injury. Interestingly, it is noted that dexamethasone treatment resembles the effect of cardiac preconditioning. The finding that dexamethasone had no significant effect on PKCd expression and activity in the heart suggests that its effect on PKCe in isozyme-selective. Studies with transgenic mice have shown that activation of PKCd increases Betaxolol injury from ischemia reperfusion and inhibition of PKCd exerts protective effect. These findings suggest that dexamethasone promotes cardioprotection through Butamben modulation of the relative ratio of PKCe to PKCd in the heart. In addition to PKC, Tokudome et al observed that glucocorticoid protected hearts from ischemia reperfusion injury by activating cyclooxygenase-2 and prostaglandin D biosynthesis. The previous study has also shown that COX-2 expression is differentially regulated by AT1R and AT2R. Perhaps glucocorticoids modulate the expression pattern of angiotensin II receptors in the heart, which produces an intracellular environment conducive for cardioprotective factors such as PKCe and COX-2 to predominate, resulting in increased protection of the heart against ischemia and reperfusion injury. Major risk factors for coronary artery disease include a cluster of conditions such as obesity, dyslipidemia, hypertension and insulin resistance that is also referred to as metabolic syndrome. Unbalanced, fat-rich diet, which is a recognized cause of the metabolic syndrome, has been reported to have direct effects on vascular tone mainly by interfering with activation of eNOS,. Thus, abnormal endothelial function is a common feature of the syndrome and is usually considered to be secondary to the metabolic abnormalities. More recently, it has been hypothesized that endothelial dysfunction may precede or even cause metabolic deregulation. Nitric oxide, a major factor in the regulation of vascular function, is believed to also exert a significant role in the maintenance of glucose homeostasis, by contributing to modulation of peripheral insulin sensitivity, and possibly insulin secretion.