Positive inotropic effect of thyrotropin-releasing hormone on isolated rat hearts

The effects of thyrotropin releasing hormone (TRH) on the contractility of electrically stimulated and perfused isolated rat hearts were investigated. TRH in the range of 0.1-10 mumol/l was found to exert a positive inotropic effect on cardiac contractility, which however qualitatively differed at lower vs. higher concentrations of the hormone: at 1 mumol/l, TRH was found to significantly enhance the rate of contraction as well as that of relaxation (by 23.2 +/- 3.7 and 27.8 +/- 7.7%, respectively), which culminated in an increased peak contractile force. However, at 10 mumol/l, the positive inotropic effect of TRH (i.e. the increase in peak contractile force) was smaller than at 1 mumol/l, which apparently was due to both a reduced TRH-induced elevation in the rate of contraction (12.4 +/- 3.2%) and a TRH-induced decrease in relaxation rate (11.1 +/- 8.1%). Since TRH is expressed in the heart, the above findings suggest that, in addition to its CNS-mediated cardiovascular effects, TRH modulates cardiac contractility as an autocrine regulator in a concentration-dependent manner, which likely involves more than one TRH receptor and associated signaling pathway.