Blood pressure and splanchnic nerve activity are reduced by a vagally mediated opioid action.

An enkephalin analogue, D-Ala2-Met5-enkephalinamide (DAME), caused a fall in blood pressure (BP) following right atrial administration (RA) in urethane-anesthetized rats that were also atropinized, paralyzed, and artificially ventilated. This reduction in BP was not related to opioid-induced bradycardia. At a dose of 250 micrograms/kg RA the maximum percentage change was -36.0 +/- 3.9% occurring within 10-15 s subsequent to administration. The fall in BP was blocked by both pretreatment with naloxone HCl (75-100 micrograms/kg i.v.) and bilateral cervical vagotomy. Similar hypotensive responses (-37.3 +/- 2.3%) were obtained with phenyldiguanide (PDG) (40 micrograms/kg RA), a known stimulant of pulmonary J receptors (pulmonary C fibers). However, unlike DAME, the PDG response could not be blocked by naloxone. The fall in BP. obtained with DAME and PDG, paralleled a reduction in the spike frequency of the greater splanchnic nerve activity. This reflex fall in activity did not involve supramesencephalic structures because results were similar in both urethane-anesthetized and unanesthetized midcollicular decerebrate preparations. It was concluded that opioids can act peripherally, via pulmonary opiate receptors, to inhibit central vasomotor activity and reduce BP by eliciting a pulmonary chemoreflex.