Expression of c-fos and Related Genes in the Rat Heart in Response to Norepinephrine

We have investigated the cellular and regional localization of Fos-like immunoreactivity (FLI) in the rat heart in response to the hypertrophic hormone norepinephrine (NE). Previous studies have demonstrated elevated c-fos mRNA levels in the rat heart following this treatment but have not shown which cell type(s) or specific chamber(s) of the heart contribute to the response in vivo, or whether Fos protein is actually produced. Administration of a single injection of NE (2.5 mg/kg) or chronic infusion of NE (100 μg/kg/h) led to an increase in Fos-like immunoreactivity in the nuclei of cardiac myocytes and vascular smooth muscle cells compared to control tissue. The response was transient with maximal immunoreactivity observed 2-3 h following treatment, falling to near basal levels in most regions of the heart after 6 h. Although all chambers of the heart contributed to the response, greatest Fos-like immunoreactivity was observed in the left atrium and left ventricle, with intermediate levels found in the septum and right ventricle, and lowest levels in the right atrium. Fos-like immunoreactivity observed in the left atrium was accompanied by elevated mRNA levels of fra-1 and fra -2 not c-fos itself indicating that a related gene product other than Fos contributed to the observed response. Experiments with the Langendorff perfused rat heart showed that NE and elevated perfusion pressure independently increased both c-fos mRNA and FLI. This work is the first evidence for a direct action NE on Fos expression in adult, as opposed to neonatal, cardiomyocytes. These results lend further support to the notion that Fos and related gene products mediate some of the hypertrophic actions of norepinephrine.