ATRIAL-NATRIURETIC-PEPTIDE ACCELERATES PROLIFERATION OF CHICK EMBRYONIC CARDIOMYOCYTES IN-VITRO

The developing embryonic heart has been reported to contain significan t levels of atrial natriuretic peptide (ANP). In this study, the role of ANP in cardiac development was evaluated using cultured cardiomyocy tes isolated from chick embryos. We analyzed the effect of ANP on cell number, DNA synthesis, total RNA level, the expression of cell-cycle- specific and sarcomeric proteins, and levels of lactate dehydrogenase and creatine phosphokinase. ANP increased overall DNA syn thesis (meas ured by BrdU incorporation, P<0.01) and enhanced cell proliferation. M orphologically, the development of the cardiomyocyte network was disti nctly enhanced in the ANP-treated cells. Cellular RNA content was elev ated; likewise, myosin and tropomyosin biosynthesis was significantly greater in ANP-treated cells. In addition, expression of G1/S-specific protein increased, whereas G2/M-specific protein remained unchanged b y ANP treatment. An antibody against ANP and a specific ANP receptor a ntagonist, HS-142-1, antagonized and/or attenuated the action of ANP o n both cell proliferation and protein biosynthesis. These results indi cate that ANP accelerates myocardial cell proliferation by enhancing e ntry into S phase and by increasing DNA synthesis during S phase speci fically through receptor mediated pathway. The in vitro effects of ANP on myocardial cell proliferation, together with the elevated levels o f ANP seen in vivo during normal heart formation, suggest a possible a utocrine function of ANP in embryonic cardiac development.