Neurotensin (NT) immunoreactivity and binding sites have been demonstrated to be extensively distributed throughout the caudal nucleus of the solitary tract (NTS). In this study, the cardiovascular effects of microinjecting the tridecapeptide neurotensin (NT) or its analogues NT 1-8 and [D-Trp11]NT into NTS were investigated in the chloralose-anesthetized, paralyzed and artificially ventilated rat. Microinjection of NT (10 pmol) elicited decreases in arterial pressure (AP) (-34 +/- 3 mm Hg) and heart rate (HR) (-28 +/- 2 beats/min), whereas microinjection of equimolar amounts of the NT fragment NT 1-8 elicited a significantly smaller depressor response (-14 +/- 3 mm Hg), but the bradycardic (-22 +/- 4 beats/min) response was similar in magnitude to that elicited by NT. On the other hand, microinjection of [D-Trp11]NT did not elicit cardiovascular responses from sites in NTS. In addition, the prior injection of [D-Trp11]NT into cardiovascular responsive sites in the NTS did not significantly reduce the AP or HR response to NT. The depressor response elicited by NT was not affected by bilateral vagotomy but was abolished by either C1-C2 spinal cord transection or the i.v. administration of the nicotinic receptor blocker hexamethonium bromide. The cardiac slowing was partially attenuated by either bilateral vagotomy (-19 +/- 2 beats/min), i.v. administration of atropine methyl bromide (-17 +/- 4 beats/min), i.v. administration of hexamethonium bromide (-11 +/- 4 beats/min) or by spinal cord transection (-12 +/- 3 beats/min), and completely abolished after total autonomic blockade or by combined bilateral vagotomy and spinal cord transection. These data have demonstrated that within a restricted region of the caudal NTS NT activates neurons that contribute to vasodepressor responses as a result of sympatho-inhibition and to bradycardia responses as a result of vagal excitation and sympatho-inhibition. Furthermore, these data suggest that NT may act as a neurotransmitter or modulator in central cardiovascular reflex pathways.