Mechanisms involved in the cardiovascular responses to opioid products of proenkephalin in the anaesthetised rat.
1. Cardiovascular effects of opioid peptide products of proenkephalin, [Met] enkephalin (ME), [Leu] enkephalin (LE), [Met] enkephalyl Arg6-Phe7 (MEAP) and [Met] enkephalyl Arg6-Gly7-Leu8 (MEAGL) have been studied in urethane-anaesthetised rats. 2. ME, LE, MEAP and MEAGL produced vasodepression and bradycardia mediated by mu-opioid receptors. 3. Atypical responses to MEAP were observed in a quarter of the animals studied showing tachycardia and pressor effects. This response was probably due to the release of the dipeptide Arg-Phe which exerted its effects at sympathetic ganglia. 4. Studies with the peptidase inhibitors captopril and bestatin showed a differential potentiation of the cardiovascular effects of the proenkephalin products by inhibition of angiotensin converting enzyme and aminopeptidase. 5. The effects of vagotomy, pithing and studies with atropine, and N-methyl levallorphan were used to demonstrate that, for all four proenkephalin peptides, cardiovascular effects were mediated by peripheral opioid receptors and transmission to the CNS via vagal afferents.
Douglas
H
H
School of Biological Sciences, University of Surrey, Guildford, England.
Kitchen
I
I
D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004723:Endorphins / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D011498:Protein Precursors; C029992:proenkephalin