Attentuation of Cardiac Stunning by Losartan in a Cellular Model of Ischemia and Reperfusion Is Accompanied by Increased Sarcoplasmic Reticulum Ca2 Stores and Prevention

This study investigates whether protective effects of an angioten-sin II type 1 receptor antagonist (losartan) in ischemia and reper-fusion are mediated by actions on Ca2 cycling. Effects of expo-sure to losartan (10 M) in ischemia were evaluated in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion at 37°C. Field-stimulatedmyocytes were exposed to 30 min of simulated ischemia (hypoxia, acidosis, lactate, hyper-kalemia, and glucose-free) and reperfusion with Tyrode’s solution for 40 min. Cell shortening was measured with a video edge detector, and Ca2 concentration was measured with fura-2. Field-stimulated myocytes exhibited stunning in reperfusion, which was abolished in cells exposed to losartan. In microelec-trode studies, losartan did not alter the responses of resting po-tentials or action potentials to ischemia and reperfusion. In th