New occurrence of atrial natriuretic factor and storage in secretorially active granules in adult rat ventricular cardiomyocytes in long-term culture.

Under normal physiological conditions atrial natriuretic factor (ANF) in rat is stored in secretory granules in fetal and adult atrial cardiomyocytes (Cantin et al., 1984; de Bold, 1985), whereas in fetal and neonatal ventricular cardiomyocytes secretory granules are practically absent and ANF is directly secreted via the constitutive pathway (Bloch et al., 1986; Cantin et al., 1987). In ventricular adult rat cardiomyocytes however, ANF is down-regulated and only expressed in cells of interventricular septum (Reinecke, 1989). These ANF-containing cells seem to constitute part of the Purkinje fibre system. As ventricular adult rat cardiomyocytes (ARC) in longterm culture in many ways re-express the fetal program (Eppenberger et al., 1988; Eppenberger-Eberhardt et al., 1990), it was of interest to investigate whether this was also the case for ANF. Data in the present study show that immunoreactive (IR) ANF is upregulated in cultured ventricular ARC and is stored just as in cultured atrial ARC in "atrial-type" granules and secreted into the medium. A possible analogy with overload heart hypertrophy in vivo, where a reactivation of an early gene program including re-expression of ANF in ventricular myocytes has been described (Izumo et al., 1987; Chien et al., 1991), is proposed.