NPY Y1 receptors are involved in cardio-respiratory responses to intravenous injection of neuropeptide Y in anaesthetized rats

The respiratory effects evoked by systemic injection of neuropeptide Y (NPY) were studied in anaesthetized, spontaneously breathing rats that were (i) neurally intact; (ii) subjected to bilateral midcervical vagotomy (MC vagi cut); (iii) midcervically vagotomized and treated by supranodosal denervation (NG vagi cut); (iv) neurally intact, before and after pharmacological blockade of the NPY Y 1 and NPY Y 2 receptors. An intravenous (iv) bolus of NPY (100 μg/kg) induced slowing down of the respiratory rate, decreased tidal volume and heart rate, and increased mean arterial blood pressure. After section of midcervical vagi, NPY still evoked the cardio-respiratory changes. Supranodose vagotomy abolished the fall in respiratory rate and reduced significantly the decreases in tidal volume and minute ventilation. This level of vagotomy did not affect vasopressor and bradycardic effects of NPY. Blockade of NPY Y 1 receptors with an intravenous dose of 5 mg/kg of BMS 193885, reduced significantly the cardio-respiratory effects of NPY injection. Pre-treatment with BIIE 0246, NPY 2 receptor antagonist at a dose of 1–2.5 mg/kg was not effective in blocking the response to NPY. The results of this study indicate that NPY-evoked activation of NPY Y 1 receptors decreases both components of the breathing pattern, and this response is primarily mediated central to the cervical vagi. Bradycardia and hypertensive effect of NPY are attributed to the excitation of peripheral and central NPY Y 1 receptors and occur outside of the vagal pathways.