Inotropic effects of endothelin compared to noradrenaline in porcine myocardial trabeculae.
Isolated porcine myocardial trabeculae from the right atria and left ventricles were paced at 1.5 Hz in tissue baths, and changes in isometric contractile force upon exposure to noradrenaline (NA), endothelin-1 (ET-1) and endothelin-3 (ET-3) were studied. The endothelin-B- (ET(B)) receptor agonists IRL 1620 and sarafotoxin S6c (S6c), and the endothelin-A- (ET(A)) receptor antagonist FR139317 were used to assess the functional involvement of ET(A)- and ET(B)-receptors. NA, ET-1 and ET-3 induced strong increases in contractile amplitude of all trabeculae. In both atrial and ventricular trabeculae the increases in contractile amplitudes induced by ET-1 and ET-3 were significantly lower than those induced by noradrenaline, whereas the potencies for ET-1 and ET-3 were significantly higher than those for noradrenaline (p < 0.05, n = 6-10 in each group). The positive inotropic effect of ET-1 was antagonized by preincubation with FR139317 (10(-6) M). IRL 1620 had a positive inotropic effect in only a few of the ventricular but in none of the atrial trabeculae, and S6c had no positive inotropic effect in either atrial or ventricular trabeculae (n = 6-9 in each group). These results suggest that positive inotropic responses can be mediated by both ET(A)- and ET(B)-receptors.
Saetrum Opgaard
O
O
Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands. osaetrum@uci.edu
Tom
B
B
de Vries
R
R
Saxena
P R
PR
Edvinsson
L
L
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D013552:Swine
D001381:Azepines; D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D007211:Indoles; D010446:Peptide Fragments; C074308:sovateltide; C079574:FR 139317; D009638:Norepinephrine