ABSTRACT
INTRODUCTION: Endothelin-1 (ET-1) has potent vasoconstrictor, growth promoting and positive inotropic properties. Its effects on the intrinsic properties of the myocardium were recently described. The present study investigated the mechanisms underlying those effects. METHODS: The myocardial effects of 1 and 10 nM of ET-1 were evaluated in isolated rabbit papillary muscles (n = 9) and human atrial trabecula from CABG patients (Krebs-Ringer; 1.8 mM CaCl2; 35 degrees C). In papillary muscles the effects of 1 nM ET-1 were also studied in the presence of: (i) a selective ETA receptor antagonist, BQ-123 (0.1 microM; n = 9); (ii) a selective ETB receptor antagonist, BQ-788 (0.1 microM; n = 6); and (iii) an Na+/H+ exchanger inhibitor, methyl-isobutyl-amiloride (MIA; 1 microM; n = 6). Only significant results (mean +/- SE, p < 0.05) are given, expressed as delta % baseline. RESULTS: In AT by papillary muscles, 1 nM of ET-1 increased 64 +/- 16%, dT/dtmin 39 +/- 13% and decreased PT by 11 +/- 2%. The analysis of atrial strip contractions yielded similar results. In papillary muscles the effects of ET-1 were not affected by BQ-788, yet they were abolished by BQ-123, and reduced by 44% by MIA. CONCLUSIONS: The action of ET-1 on myocardial function is similar in human and non-human myocardium. The myocardial effects observed in the present study are mediated by the binding to ETA receptors, and partially dependent on Na+/H+ exchanger activation.
