Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids.
We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systemically) at maximal effect of D-Ala-D-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or VT/TTOT decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on VT/TTOT and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE decreases heart rate by increasing parasympathetic activity to the heart and induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either direct opioid action on central respiratory regulation or parasympathetic non-muscarinic or non-cholinergic mediating mechanisms.
D000818:Animals; D001158:Arteries; D001285:Atropine / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009407:Nerve Block; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects*
D004745:Enkephalins; D002245:Carbon Dioxide; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D001285:Atropine