Cardiovascular mechanisms of thyrotropin-releasing hormone against experimental hemorrhagic shock

Abstract

Thyrotropin-releasing hormone (TRH) improved mean arterial pressure (MAP) and myocardial contractility (dp/dtmax, -dp/dtmax, Vpm, and Vmax) and increased plasma epinephrine levels significantly at 10 min after TRH treatment in rabbits following shock, but the effects of TRH on MAP and myocardial contractility disappeared in reserpinized rabbits (4 mg/kg, 24 hr pre-treatment, iv). TRH had no effect on myocardial contractility and MAP at 20 and 30 min post-treatment in rabbits pre-treated with the beta adrenergic blocker propranolol (1 mg/kg, 1 hr before TRH treatment, iv), but the alpha adrenergic blocker phenoxybenzamine did not affect these responses to TRH. Experiments in vitro show that although TRH (10(-3) to 10(-8) M) had no direct effects on the isolated heart, left atrium, and aortic strip, it did potentiate the inotropic effects of isoprenaline and dopamine on the left atrium. These results suggest that the antishock effects of TRH are related to adrenergic systems, perhaps acting on the sympathomedullary system to secrete epinephrine and sensitize the beta receptors, but not alpha receptors. Thus, TRH improves cardiac contractility, cardiac output, and hemodynamics during hemorrhagic shock. The sensitization of the beta adrenergic and dopamine receptors may play an important role in the direct peripheral cardiovascular mechanism of TRH effects.