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.