Recently, we defined an 1A-adrenergic receptor-ERK (1A-AR-ERK) survival signaling pathway in adult cardiac myocytes. Previous studies in neonatal cardiac myocytes indicated that the cardiac-specific transcription factor GATA4 is a downstream mediator of 1-ERK signaling and that phosphorylation of GATA4 by ERK increases DNA binding and transcriptional activity. Therefore, we examined GATA4 as a potential downstream effector of 1A-ERK survival signaling in adult cardiac myocytes. We measured norepinephrine (NE)-induced cell death in cultured cardiac myocytes lacking 1-ARs (cultured from 1A/B-AR double knockout mice, 1ABKO mice) that are susceptible to cell death induced by several pro-apoptotic stimuli including NE. Our results show that overexpression of GATA4 is sufficient to protect 1ABKO cardiac myocytes from NE-induced cell death. However, we found that the 1A-subtype did not induce phosphorylation or increase the activity of GATA4 in adult mouse cardiac myocytes in culture or in vivo. Furthermore, we examined the effect of siRNA-mediated knockdown of GATA4 on 1A-survival signaling. In 1B-knockout cardiac myocytes, which express only the 1A-subtype and are protected from NE-induced cell death, GATA4 knockdown did not reverse 1A-survival signaling in response to NE. In summary, we found that GATA4 acted as a survival factor by preventing cell death in 1ABKO cardiac myocytes, but GATA4 was not activated by 1-AR stimulation and was not required for 1A-survival signaling in adult cardiac myocytes. This also identifies an important mechanistic difference in 1-signaling between adult and neonatal cardiac myocytes.