Pulmonary opiate receptor activation evokes a cardiorespiratory reflex

Area of Science:

• Cardiovascular physiology
• Respiratory physiology
• Neuropharmacology

Background:

• Enkephalins are endogenous opioid peptides with diverse physiological roles.
• The cardiovascular and respiratory effects of enkephalins are not fully understood.
• Pulmonary vagal afferents play a critical role in regulating cardiorespiratory function.

Purpose of the Study:

• To investigate the cardiorespiratory effects of enkephalin analogues in decerebrate rats.
• To elucidate the neural pathways mediating these effects.
• To identify the specific pulmonary receptors involved.

Main Methods:

• Administration of [D-Ala2,Met5]enkephalinamide (D-AME) and [D-Ala2,Leu5]enkephalinamide (D-ALE) into the right atrium of decerebrate rats.
• Monitoring of heart rate, blood pressure, respiratory activity, phrenic nerve (PN) activity, and recurrent laryngeal nerve (RLN) activity.
• Pharmacological blockade with naloxone and atropine.
• Surgical manipulation of vagi (sectioning at different levels).
• Recording of pulmonary vagal afferent activity.

Main Results:

• D-AME and D-ALE induced dose-dependent bradycardia, transient blood pressure changes, and apnea, followed by rapid shallow breathing.
• These effects were blocked by naloxone and atropine (for bradycardia).
• Bivagotomy below cardiac branches abolished the responses, indicating a vagal reflex originating in the lungs.
• In ventilated animals, enkephalin analogues inhibited PN activity and excited RLN activity.
• Pulmonary type J-receptors were stimulated, while stretch and irritant receptors were unaffected.

Conclusions:

• Enkephalin analogues trigger a lung vagal afferent reflex causing cardiorespiratory changes.
• The reflex involves stimulation of pulmonary type J-receptors.
• This reflex pathway contributes to the central regulation of cardiorespiratory function.