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.
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology*; D013153:Splanchnic Nerves / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D001645:Biguanides; D011957:Receptors, Opioid; D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C008846:phenyl biguanide