C-fos expression and protein kinase C translocation are mediated by α-agonist but not by angiotensin II stimulation in vivo.

Translocation of protein kinase C (PKC) from the cytosolic to particulate fraction is associated with c-fos gene expression and increased protein synthesis in the neonatal cardiocyte, but a link between receptor-mediated intracellular signals and gene expression in the intact adult rat heart is undefined. We gave continuous intravenous infusions of angiotensin II (AII; 400 ng/kg/min), phenylephrine (PHE; 10 μg/kg/min), or methoxamine (MTX; 100 μg/kg/min) to elicit comparable arterial pressures (BP=184, 184, and 183 mmHg in AII, MTX, and PHE, respectively) in conscious adult rats for 10 to 45 min. Control (CON) rats were infused with saline (50 μl/min) for similar durations. The fraction of total PKC-ε in the particulate compartment of MTX (60%), PHE (55%), and AII (65%) was greater than CON (31%). In contrast c-fos mRNA expression increased 5-10 fold in MTX and PHE but was unchanged in AII. Thus, c-fos expression can be dissociated from PKC-ε translocation and increased BP in the intact adult heart exposed to AII. This suggests that α-adrenergic and not AT1 mediated pathways are relevant in the activation of early response genes in the adult heart.