Neurotensin stimulates histamine release from the isolated, spontaneously beating heart of rats

Abstract Neurotensin (NT) evoked a transient, dose-dependent histamine release (ED 50 170 ng ml −1 ) from the rat perfused heart. Histamine release by NT occurred within seconds and lasted less than 2 min. The histamine releasing effect of NT was followed by a dose-dependent increase of the perfusion pressure and a slight tachycardis. The histamine releasing effect of NT was completely abolished in hearts derived from rats pretreated for 3 days with high doses of compound 48 80 . The coronary vasoconstrictor effect of NT was increased in hearts derived from compound 48 80 - pretreated rats. The mast cell inhibitor cromoglycate markedly inhibited NT-induced histamine release without affecting the coronary vasoconstrictor effect of NT. The histamine releasing effect of NT was inhibited, while its coronary vasoconstrictor effect was markedly potentiated, in hearts derived from rats pretreated with the antiallergic and anti inflammatory steroid dexamethasone. The increase of perfusion pressure evoked by NT was not modified by antihistaminic drugs. Infusions of exogenous histamine (10 −6 - 10 −5 g ml −1 ) caused a dose-dependent coronary vasodilation in the rat perfused heart. The results suggest that NT stimulates histamine release from cardiac mast cells. These results together with those obtained in previous studies suggest that mast cell mediators (particularly histamine and serotonin) are unlikely to be responsible for the coronary vasoconstrictor effect of NT in the rat perfused heart.