Synergistic activation of salmon cardiac function by endothelin and beta-adrenergic stimulation

The aim was to find out the effects of endothelin-1 (ET-1) in salmon (Salmo salar) cardiac contractile and endocrine function and its possible interaction with beta-adrenergic regulation. We found that ET-1 has a positive inotropic effect in salmon heart. ET-1 (30 nM) increased the contraction amplitude 17+/-4.7% compared with the basal level. beta-Adrenergic activation (isoprenaline, 100 nM) increased contraction amplitude 30+/-13.1%, but it did not affect the contractile response to ET-1. ET-1 (10 nM) stimulated the secretion of salmon cardiac natriuretic peptide (sCP) from isolated salmon ventricle (3.3+/-0.14-fold compared with control) but did not have any effect on ventricular sCP mRNA. Isoprenaline alone (0.1-1,000 nM) did not stimulate sCP release, but ET-1 (10 nM) together with isoprenaline (0.1 nM) caused a significantly greater increase of sCP release than ET-1 alone (5.4+/-0.07 vs. 3.3+/-0.14 times increase compared with control). The effects on the contractile and secretory function could be inhibited by a selective ETA-receptor antagonist BQ-610 (1 microM), whereas ETB-receptor blockage (by 100 nM BQ-788) enhanced the secretory response. Thus ET-1 is a phylogenetically conserved regulator of cardiac function, which has synergistic action with beta-adrenergic stimulation. The modulatory effects of ET-1 may therefore be especially important in situations with high beta-adrenergic tone.