Abstract 1595: Positive Inotropic Effect Of Relaxin-2 In Atrial Myocardium Of Terminally Failing Hearts: Role Of Protein Kinase A And Potassium Channels
The insulin-like peptide relaxin, a pregnancy hormone, exerts anti-fibrotic, renal, central nervous, and vascular effects, and is a positive inotropic agent in rat atrial myocardium. We have recently demonstrated that relaxin acts as compensatory mediator in human heart failure. This is the first investigation of the inotropic effects of relaxin-2 in human myocardium. We used human right and left atrial as well as right and left ventricular myocardial samples obtained from donor hearts that were not transplanted for technical reasons (n=5) and from explanted, terminally failing hearts (n=8; 4 patients with dilated cardiomyopathy, 4 patients with ischemic cardiomyopathy). In right and left atrial preparations from both donor and failing hearts, human relaxin-2 evoked positive inotropic effects (EC50 of peak developed tension for isometric twitches; donor, 0.5 ± 0.1 nM [right atrium] and 0.6 ± 0.1 nM [left atrium]; failing, 0.6 ± 0.1 nM [right atrium] and 0.6 ± 0.1 nM [left atrium]; maximum peak developed tension in percent of baseline; donor, 283 ± 35 % [right atrium] and 267 ± 30 % [left atrium]; failing, 258 ± 38 % [right atrium] and 268 ± 34 % [left atrium]). These effects could be prevented by treatment with the protein kinase A inhibitor 5–24 amide and with glibenclamide, a blocker of ATP-sensitive potassium channels. Staurosporine, a protein kinase C inhibitor, and KT-5823, a protein kinase G inhibitor, had no effects. On the other hand, a positive inotropic effect of relaxin-2 could be found neither in donor nor in failing right and left ventricular myocardium although all preparations showed similar inotropic responses to increased extracellular calcium concentrations. In conclusion, our findings indicate that the positive inotropic atrial effect of human relaxin-2 is well preserved in terminally failing human myocardium. The effect is mediated via protein kinase A and ATP-sensitive potassium channels. In ventricular myocardium, there is no such inotropic action of relaxin.