Effect of endorphins on heart rate and blood pressure in adult dogs.
To investigate the role of opioids in regulating cardiovascular function, we administered delta-opioid receptor agonists D-Ala-D-Leu enkephalin (DADLE) and D-Ala-Met enkephalinamide (DAME), and mu-opioid receptor agonist, a morphiceptin analogue (MA), intracisternally in 13 unanesthetized, chronically instrumented adult dogs in 2 doses (25 and 125 micrograms/kg). After an initial transient drop, the R-R interval increased (peak approximately 25-60 min) postadministration of opioids. The time course and the magnitude of the change in R-R interval depended on the agonist: delta-agonists induced a more prolonged and marked change in R-R interval than mu-agonists at both doses. Mean arterial blood pressure (MAP) increased initially but dropped toward or even below base line 30 min after opioids administration. Atropine, given intravenously or intra-arterially at peak action of agonist in relatively low doses (0.02 mg/kg), induced an AV block followed by a marked decrease in R-R interval. There was also an increase in MAP after atropine. Naloxone, given intracisternally, reversed both delta- and mu-opioid effects but did not induce changes in the R-R interval without prior administration of opioids. We conclude that in unanesthetized adult dogs 1) both mu- and delta-receptor opioid agonists prolong the R-R interval, and this depends on the type of receptor stimulated; 2) opioids induce slowing in heart rate, possibly by increasing parasympathetic activity to the heart; 3) enkephalin and morphiceptin analogues induce a biphasic response in MAP; and 4) endorphins do not modulate cardiovascular function tonically; we speculate that they can alter the R-R interval and MAP in the presence of stimuli.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness / Q000187:drug effects; D004285:Dogs; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology
D004723:Endorphins; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C022118:enkephalinamide-Met, Ala(2)-; D016308:Enkephalin, Leucine-2-Alanine; D001285:Atropine; C028889:morphiceptin