alpha(l)-Adrenergic stimulation of FGF-2 promoter in cardiac myocytes and in adult transgenic mouse hearts

Fibroblast growth factor (FGF-2), a mitogenic, angiogenic, and cardioprotec tive agent, is reported to be released from the postnatal heart by a mechan ism of transient remodeling of the sarcolemma during contraction. This rele ase can be increased with adrenergic stimulation. RNA blotting was used to assess whether FGF-2 synthesis in neonatal rat cardiomyocytes might also be regulated by adrenergic stimulation. FGF-S RNA levels were increased after treatment with norepinephrine for 6 h or with the oc-adrenergic agonist ph enylephrine for 48 h. To assess an effect on transcription, neonatal rat ca rdiomyocytes were transfected with a hybrid rat FGF-2 promoter/luciferase g ene (-1058FGFp.luc) and treated with norepinephrine or phenylephrine for 6 or 48 h, respectively. FGF-2 promoter activity was increased two- to sevenf old in an al-specific manner. Putative phenylephrine-responsive elements (P EREs) were identified at positions -780 and -761 relative to a major transc ription initiation site. However, deletion analysis of -1058FGFp.luc showed that the phenylephrine response was independent of the putative PEREs, cel l contraction, and Ca2+ influx. In transgenic mice expressing -1058FGFp.luc , a significant three- to sevenfold stimulation of FGF-2 promoter activity was detected in the hearts of two independent lines 6 h after intraperitone al administration of phenylephrine (50 mg/kg). This increase was still appa rent at 24 h but was not detected at 48 h posttreatment. Analysis of FGF-2 mRNA in normal mouse hearts revealed accumulation of the 6.1-kb transcript at 24 h. Control of local FGF-2 synthesis at the transcriptional level thro ugh adrenergic stimulation may be important in the response to injury as we ll as in the maintenance of a healthy myocardium.