Mechanism of neurotensin-induced pressor effect and tachycardia in guinea pigs

Neurotensin (NT) was found to produce a dose-dependent increase of the systolic and diastolic blood pressure, and of the heart rate in anesthetized guinea pigs when injected intravenously (i.v.) as a bolus, or when infused i.v. over a 15 min period. In a small percentage (20%) of animals, bolus injections of NT evoked triphasic variations (e.g. increase followed by a decrease and a further increase) of the blood pressure associated with unpredictable changes of heart rate. The pressor effect of NT was consistently reduced by prior treatment of the animals with pentolinium, a ganglion blocking agent, a mixture of alpha and beta adrenergic receptor blocking drugs, reserpine, a drug known to deplete adrenergic neurons of their neurotransmitters, or guanethidine, a drug known to paralyse adrenergic neurons. NT-induced tachycardia was either unchanged or slightly potentiated following the administration of the latter autonomic blockers. Neither the pressor effect nor the tachycardia evoked by NT was affected by antihistaminics, antiangiotensin or by indomethacin, an inhibitor of prostaglandin synthesis. These results suggest that the pressor effect of NT in anesthetized guinea pigs is likely the result of an interaction (most likely an activation) between the peptide and the sympathetic nervous system. The increase of heart rate induced by NT appears to be due to a direct effect on the heart.