AT(1) RECEPTOR BLOCKADE IN EXPERIMENTAL MYOCARDIAL ISCHEMIA REPERFUSION/

The renin-angiotensin system is activated during myocardial ischemia, and local angiotensin II formation occurs in ischemic hearts. At least two angiotensin II receptor subtypes, the AT(1) and AT(2) receptor, h ave been identified. The cardiovascular effects of angiotensin II have been largely attributed to activation of AT(1) receptors. In ventricu lar preparations from normal rat and pig hearts, the density of AT(1) receptors is higher than that of AT(2) receptors, whereas data on the AT receptor subtype density and its distribution in human hearts remai n controversial. AT(1) receptor blockade increases coronary blood flow during ischemia in dogs and during reperfusion in rats. It also reduc es the incidence of ischemia-related arrhythmias in rats and guinea pi gs, Limits infarct size in pigs, improves functional and metabolic rec overy following myocardial ischemia, and attenuates ventricular remode lling post-myocardial infarction in rats. The potential mechanisms res ponsible for the cardioprotection by AT(1) receptor blockade remain to be elucidated in detail, but appear to involve AT(2) receptor activat ion and the subsequent action of bradykinin, prostaglandins, and/or ni tric oxide.Patients under treatment with AT(1) receptor antagonists fo r indications such as hypertension and ventricular dilatation after my ocardial infarction are likely to have improved prognosis when sufferi ng an acute myocardial infarction.