Alpha 1A Aderenergic Receptors Enhance Contractile Function of the Ischemic Heart
Three alpha 1-AR subtypes (alpha 1A-, alpha 1B-, alpha 1D-AR) have been cloned and characterized. However, the currently available ligands do not have sufficient subtype selectivity to unequivocally identify the functions of each alpha 1-AR subtype. Therefore, their functions must be identified using alternative methods. Previous studies have demonstrated that alpha 1-ARs protect the heart from ischemic injury. The goal of the present study was to determine whether mice that express constitutively active mutant (CAM) alpha 1A-ARs are protected from ischemic injury. Hearts isolated from nontransgenic or CAM alpha 1A-AR mice were perfused using the Langendorf method. Hearts were perfused for 1 hour, subjected to 30 min ischemia, and reperfused for 1 hour. Contractile function was continuously monitored by an intraventricular balloon connected to a pressure transducer and a digital data acquisition system. Tissue necrosis was assessed by measuring lactate dehydrogenase (LDH) activity in the cardiac perfusate immediately before and after ischemia. We found that postischemic recovery of contractile function was significantly increased in CAM alpha 1A-AR hearts compared to nontransgenic hearts. However, LDH activity was similar in both groups. Our data suggest that alpha 1A-AR signaling enhances postischemic contractile function of the myocardium but does not limit tissue necrosis.