IGF-I AND BFGF DIFFERENTIALLY INFLUENCE ATRIAL-NATRIURETIC-FACTOR ANDALPHA-SMOOTH MUSCLE ACTIN EXPRESSION IN CULTURED ATRIAL COMPARED TO VENTRICULAR ADULT-RAT CARDIOMYOCYTES

In the present study, we compare expression, storage and secretion of the atrial natriuretic factor (ANF) in atrial and ventricular adult ra t cardiomyocytes (aARC and vARC) in long-term culture, The influence o f insulin-like growth factor-I (IGF-I) and of basic fibroblast growth factor (bFGF) on ANF production and secretion, as well as on the expre ssion of a structural component, alpha-smooth muscle actin (alpha-sm a ctin), was studied in the two cell types. Antibodies against alpha-ANF were used for immunocytochemical localization of ANF. aARC contained more ANF-granules than vARC, and they were distributed throughout the cell bodies. Quantitative determination of ANF storage and secretion w as done by radioimmunoassay (RIA; I-125), and it was demonstrated that aARC stored and secreted ANF 18- and 16-times more, respectively, whe n compared to vARC, Immuno-electron microscopy confirmed that ANF stor ing secretory granules were present in both types of cardiomyocytes. E xpression of ANF and alpha-sm actin in aARC and vARC responded differe ntly to treatment with either IGF-I or bFGF. In aARC, neither IGF-I no r bFGF had an influence on expression of ANF. In vARC, expression of A NF was down-regulated by IGF-I and upregulated by bFGF with regard to both immunoreactivity and message. In contrast to vARC, expression of alpha-sm actin was not affected by IGF-I in aARC, whereas bFGF produce d a strong upregulation similar to that found in vARC. Mitogen-activat ed protein kinases (MAPK) 42 and 44, though, were equally activated by bFGF and IGF-I in both aARC and vARC. (C) 1997 Academic Press Limited .