POSITIVE INOTROPIC EFFECT OF THYROTROPIN-RELEASING-HORMONE ON ISOLATED RAT HEARTS

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