Interaction of thyrotropin-releasing hormone (TRH) and serotonin in cardiovascular control

Intravenous injection of the synthetic TRH analog, MK-771, to anesthetised cats raised the blood pressure by a central mechanism, i.e. by activating the outflow of sympathetic stimuli from the CNS to the periphery and raising the plasma concentration of adrenaline and noradrenaline. In contrast, noradrenaline in the CSF was lowered by intravenously injected MK-771. The concentration of 5-HT in the CSF was increased and the pressor action of the peptide was correspondingly enhanced by 5-HT antagonists. These findings suggest that the release of 5-HT into the CSF lowers blood pressure and thus reduces the hypertensive effect of MK-771. Methysergide acts synergistically with MK-771 to combat the sudden fall in pressure induced by acute hemorrhage in the anesthetised cat. Combination of the two drugs enhanced and accelerated recovery from this hypotensive state.