**4. Angiotensin receptor blockers (ARBs)**

ARBs preferentially block AT1 and leave AT2 unopposed. Long-term administration of ARBs results in a several-fold increase in plasma Ang and thus a possible overstimulation of AT2. It is generally accepted that the effects of stimulation of AT2 on the cardiovascular system are beneficial and that no harm would result from increased activation of these receptors; indeed, activation of AT2 is believed to contribute to the benefits of blocking AT1 (Levy, 2004).

Various ARBs were screened for their role in the treatment of acute myocarditis and are found to have significant activity against acute myocarditis. ARBs prevent progression of systolic heart failure, thereby reducing cardiac morbidity and mortality (Lindholm et al., 2002; Cohn & Tognoni, 2001). They also reduce myocardial damage during myocarditis. The major cardiovascular actions of Ang II have been reported to be mediated by the AT1, and AT1 antagonists are therapeutically effective for the treatment of patients with heart failure by reducing cytokines and oxidative stress through their anti-inflammatory effects. Thus, the blockade of AT1 is an important way to interrupt the RAS (Sukumaran et al., 2010). Recently, an AT1 antagonist has been shown to ameliorate EAM by the suppression of myocardial damage and inflammatory events in the myocardium in addition to hemodynamic modifications, and it has been reported to inhibit nitric oxide (NO) production in macrophages and IL 1 production. ARB treatment decreased myocardial fibrosis and its marker molecules (i.e. RNA expression of TGF-1 and collagen-III), and improved the survival rate and cardiac function in rats with DCM after myocarditis in a dose dependent manner. Treatment with oral ARB improved both systolic and diastolic functions, increased neurohormonal parameter, such as plasma Ang II, and ameliorated myocardial remodeling and its marker molecules (Sukumaran et al., 2010, 2011a, 2011b; Shirai et al., 2005).
