Pulmonary , gastrointestinal and urogenital pharmacology Cardiorespiratory effects of systemic neurotensin injection are mediated through activation of neurotensin NTS 1 receptors

The purpose of our study was to determine the cardio-respiratory pattern exerted by the systemic injection of neurotensin, contribution of neurotensin NTS1 receptors and the neural pathways mediating the responses. The effects of an intravenous injection (i.v.) of neurotensin were investigated in anaesthetized, spontaneously breathing rats in following experimental schemes: (i) control animals before and after midcervical vagotomy; (ii) in three separate subgroups of rats: neurally intact, vagotomized at supranodosal level and initially midcervically vagotomized exposed to section of the carotid sinus nerves (CSNs); (iii) in the intact rats 2 minutes after blockade of neurotensin NTS1 receptors with SR 142948. Intravenous injection of 10 mg/kg of neurotensin in the intact rats evoked prompt increase in the respiratory rate followed by a prolonged slowing down coupled with augmented tidal volume. Midcervical vagotomy precluded the effects of neurotensin on the frequency of breathing, while CSNs section reduced the increase in tidal volume. In all the neural states neurotensin caused significant fall in mean arterial blood pressure preceded by prompt hypertensive response. The cardiorespiratory effects of neurotensin were blocked by pre-treatment with NTS1 receptor antagonist. The results of this study showed that neurotensin acting through NTS1 receptors augments the tidal component of the breathing pattern in a large portion via carotid body afferentation whereas the respiratory timing response to neurotensin depends entirely on the intact midcervical vagi. Blood pressure effects evoked by an intravenous neurotensin occur outside vagal and CSNs pathways and might result from activation of the peripheral vascular NTS1 receptors. & 2012 Elsevier B.V. All rights reserved.