Pulmonary vagal afferent stimulants in the conscious rat: Opioids and phenyldiguanide

Phenyldiguanide (PDG, 40 μg/kg), D-ala²-met⁵-enkephalinamide (D-AME, 250 μg/kg) and morphine sulfate (MS, 2 mg/kg) injected into the right atrium (RA) of conscious freely moving rats produced a profound bradycardia and hypotension 1-2 sec subsequent to administration. Concomitant with the cardiovascular effects apnea occurred and lasted approximately 5 sec. Atropine methyl nitrate (2 mg/kg, RA) significantly attenuated the bradycardia and hypotension produced by all three agents. Naloxone blocked only the opioid responses. Coordinated motor activity was impaired following the administration of PDG (40 μg/kg, RA). Fifty percent of the animals receiving PDG failed to remain on a rotor rod for a 2 min period. Only 8 percent of the saline treated group fell off during this period. It was concluded that the cardiovascular, respiratory, and motor effects caused by PDG, in the conscious freely moving rat, were the result of stimulation of pulmonary vagal afferents (J-receptors). The cardiovascular effects of opioids are also believed to arise from the stimulation of J-receptors. However, unlike PDG, these effects are mediated by pulmonary opiate receptors.