The Effects of Opioid Peptides on Cardiovascular Function and Sympathetic Neurotransmission in Rats

M. A. Mcintosh, K. A. Kane, J. R. Parratt

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The haemodynamic effects of three opioid receptor agonists, with some preferential activity on δ‐, μ‐ and κ‐receptors were investigated in anaesthetized and pithed rats, and effects on sympathetic neurotransmission were also investigated in pithed rats. In anaesthetized rats, d‐Ala2‐d‐Leu5‐enkephalin (DADLE) (a predominantly δ‐receptor agonist, 10 μg kg−1), glyol (μ, 0·5 mg kg−1) and R,S‐N‐C2‐N‐methyl‐3,4,dichloro‐phenylacetamido‐2‐C3‐carboxy phenylethyl‐pyrrolidine (ICI 204448) (·, 0·1 mg kg−1) by intravenous administration transiently decreased heart rate from 462 ± 12 to 432 ± 14, 460 ± 12 to 448 ± 13 and 460 ± 12 to 448 ± 11 beats min−1, respectively, and mean arterial blood pressure from 142 ± 6 to 111 ± 9, 141 ± 6 to 122 ± 5 and 148 ± 7 to 121 ± 6 mmHg, respectively. The effects of DADLE, but not those of glyol or ICI 204448, were blocked by M8008, a δ‐receptor antagonist. In pithed rats, none of the opioid agonists had any significant effects on heart rate or mean arterial blood pressure; however, acetylcholine significantly reduced both heart rate and mean arterial blood pressure. All three opioid agonists reduced the positive chronotropic response to thoracic (C7‐T2) spinal cord stimulation in pithed rats, by 17 ± 4,30 ± 2 and 20 ± 10% for DADLE, glyol and ICI 204448, respectively. This compared with a 48 ± 15% reduction with clonidine (5 μ kg−1). This effect of DADLE was almost abolished by M8008. It is concluded that the haemodynamic effects of the opioid agonists studied are mediated via actions on the central nervous system and that a decrease in sympathetic neurotransmission may account for, at least in part, the bradycardia produced by opioid agonists in intact anaesthetized rats. It seems that the sympathetic nervous system is unlikely to be involved in the arrhythmogenic effects of opioid peptides. 1995 Royal Pharmaceutical Society of Great Britain

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Issue number1
Publication statusPublished - Jan 1995

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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