Expression of Active α_1B-Adrenergic Receptors in the Heart does not Alleviate Ischemic Reperfusion Injury

Abstract

X.-M. Gao, B.-H. Wang, E. Woodcock and X.-J. Du. Expression of Activeα_1B -Adrenergic Receptors in the Heart does not Alleviate Ischemic Reperfusion Injury. Journal of Molecular and Cellular Cardiology (2000) 32, 1679–1686. Ischemic preconditioning reduces infarct size and improves cardiac function in various species, including mice. The mechanism for ischemic preconditioning protection is not entirely clear and activation of α_1B-adrenergic receptors (AR) is believed to be involved. Transgenic mice expressing constitutively active mutant α_1B-AR in the heart have enhanced α_1B-AR activity and therefore can be used to test the role of α_1B-AR in ischemic preconditioning. Wild-type and transgenic mice were subjected to 30- or 40-min periods of left coronary artery occlusion followed by 60-min reperfusion, or ischemic preconditioning prior to sustained ischemia–reperfusion. Risk and infarct zones were determined by staining with Evans blue and triphenyltetrazolium, respectively, and quantitated digitally. Infarct zone and infarct size were not different between wild-type and transgenic mice, nor was the extent of reduction in infarct size by preconditioning ischemia (wild-type mice: 45±3 to 18±3%, transgenic mice: 46±3 to 19±2% of the left ventricle, bothP <0.01). Ventricular function was similar between wild-type and transgenic mice with or without ischemia–reperfusion injury. In conclusion, enhanced α_1B-AR activity by cardiac-specific expression of constitutively active mutant α_1B-AR in mice does not mimic ischemic preconditioning to protect against ischemia–reperfusion injury.