Acute effects of intravenous capsaicin on breathing rate, heart rate and blood gases in anesthetized mice with and without atropine and mechanical ventilation

The airways are densely innervated by irritant-sensitive vagal afferent nerves whose activation evokes acute modulation of respiration and heart rate. Studies in larger mammals show that the irritant capsaicin (i.v.) evokes a triple response of rapid shallow breathing (RSB), apnea, and bradycardia. Here, we studied cardiopulmonary reflexes in anesthetized mice (freely-breathing or ventilated), with and without pretreatment with the muscarinic inhibitor atropine (2mg/kg, i.p.), measuring ECG, diaphragmatic EMG (dEMG), mixed expired CO 2 (mECO 2 ), and oxygen saturation (SpO 2 ) in response to 50ml i.v. injection of vehicle or capsaicin (3ug/ml). Under all conditions, vehicle evoked no change in parameters other than a mild and transient tachycardia. In freely-breathing mice without atropine, capsaicin evoked immediate and dramatic bradycardia and bradypnea (with decreased dEMG amplitudes). RSB was often observed after the bradypnea. Capsaicin also reduced peak mECO 2 for individual breaths but had no effect on SpO 2 . mECO 2 reductions never occurred prior to the onset of bradycardia or bradypnea. Atropine significantly inhibited capsaicin-evoked bradycardia and abolished capsaicin-evoked reductions in peak mECO 2 , without reducing capsaicin-evoked bradypnea. In ventilated mice without atropine, capsaicin evoked immediate and dramatic bradycardia. Capsaicin also reduced peak mECO 2 (although less than in freely-breathing mice) but had no effect on SpO 2 . In ventilated mice, atropine significantly inhibited capsaicin-evoked bradycardia and abolished capsaicin-evoked reductions in peak mECO 2 . These data suggest that capsaicin-evoked cardiopulmonary reflexes are independent of SpO 2 , and that capsaicin-evoked decreases in mECO 2 are a consequence rather than the cause of capsaicin-evoked bradycardia and bradypnea. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.