INTERACTIONS BETWEEN ENDOTHELIN-1 AND ATRIAL-NATRIURETIC-PEPTIDE INFLUENCE CULTURED CHICK CARDIAC MYOCYTE CONTRACTILITY

We have previously shown that rat atrial natriuretic peptide (ANP) red uces the contractility of cultured, spontaneously beating chick embryo ventricular cells, an effect opposite to that of endothelin-1. Endoth elin-1 has been described as a secretagogue for natriuretic peptides i n vitro and in vivo. Natriuretic peptides can inhibit endothelin-1 sec retion from cultured endothelial cells, suggesting a negative feedback mechanism between endothelial cells and cardiomyocytes. The aim of th is study was to determine whether ANP attenuated the endothelin-1-indu ced increase in myocyte contractility. Using a video-microscopy system we studied the contractility of isolated cultured chick ventricular m yocytes in response to endothelin-1, chicken natriuretic peptide (ChNP ), and both. We also used Northern blot analysis to study the time cou rse of ChNP expression in response to endothelin-1. Endothelin-1 (10(- 8) M) increased chick cardiomyocyte contractility by 20-25% between 5 and 15 min (P < 0.05). Although ChNP (3 X 10(-7) M) did not significan tly change the amplitude of contraction in basal conditions, it preven ted the endothelin-1-induced increase in contractility (P < 0.05) when perfused prior to endothelin-1, and reversed it when perfused 5 min a fter endothelin-1 exposure (P < 0.05). Endothelin-1 significantly incr eased the accumulation of ChNP mRNA in chick ventricular myocytes as e arly as the 30 min after exposure (P < 0.05), with a maximal effect af ter 2 h of stimulation (P < 0.01); no effect was observed after 4 h. T hese data support an interaction between endothelin-1 and natriuretic peptides as autocrine/paracrine factors regulating the contractile fun ction of chick cardiac myocytes, as well as their antagonistic effects on cardiac cell contractility. The early and transient expression of ChNP mRNA in response to endothelin-1 may be involved in this interact ion.