We recently characterized from salmon a novel natriuretic hormone, salmon cardiac peptide (sCP). The effects, structure and regulation of sCP resemble those of mammalian natriuretic peptides. In this study we wanted to find out the role of endothelin-1 (ET-1) in salmon cardiac function, and the interactions between two major regulators of cardiac function, ET-1 and beta-adrenergic stimulation. We tested these ideas by monitoring perfused isolated salmon myocardium contractile function and by measuring sCP secretion from salmon heart in response to ET-1 and beta-adrenergic stimulation (isoprenaline). We found that ET-1 has a positive inotropic effect in salmon heart. ET-1 (30 nM) increased the contraction amplitude 17%. Isoprenaline (100 nM) increased contraction amplitude 30%, but it did not affect the contractile response to ET-1. ET-1 (10 nM) stimulated the secretion of sCP from isolated salmon ventricle (3.3 -fold) but did not have any effect on ventricular sCP mRNA. Isoprenaline alone (0.1-1000 nM) did not stimulate sCP release, but ET-1 (10 nM) together with isoprenaline (0.1 nM) caused a greater increase of sCP release than ET-1 alone (5.4 vs. 3.3 times increase). The cardiac responses could be inhibited by an ET_A receptor antagonist BQ-610 (1 ?mM). ET_B receptor blockage (by 100 nM BQ-788) enhanced the secretory response. Thus, ET-1 is a phylogenetically conserved regulator of cardiac function, which has a synergistic action with beta-adrenergic stimulation. The modulatory effects of ET-1 may therefore be important in situations with high beta-adrenergic tone.