Morphine is an arteriolar vasodilator in man

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • It has been recognized for about 10 years that morphine is a veno‐dilator in man and that this effect may be related to histamine release. WHAT THIS PAPER ADDS • This effect also occurs in the arteriolar system, with vasodilatation at doses of morphine that...

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Bibliographic Details
Published in:British journal of clinical pharmacology Vol. 67; no. 4; pp. 386 - 393
Main Authors: Afshari, Reza, Maxwell, Simon R. J., Webb, David J., Bateman, D. Nicholas
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01.04.2009
Blackwell Science Inc
Subjects:
Adult
Dose-Response Relationship, Drug
Forearm - blood supply
histamine
Histamine - pharmacology
Humans
Infusions, Intra-Arterial
Male
Middle Aged
morphine
Morphine - administration & dosage
Morphine - pharmacology
naloxone
nitric oxide
opioid
Pharmacodynamics
Plethysmography - drug effects
Regional Blood Flow - drug effects
Regional Blood Flow - physiology
Treatment Outcome
vasodilatation
Vasodilation - drug effects
Vasodilation - physiology
Vasodilator Agents - pharmacology
Young Adult
ISSN:0306-5251, 1365-2125, 1365-2125
Online Access:Get full text
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Summary:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • It has been recognized for about 10 years that morphine is a veno‐dilator in man and that this effect may be related to histamine release. WHAT THIS PAPER ADDS • This effect also occurs in the arteriolar system, with vasodilatation at doses of morphine that may have clinical relevance in patients with heart failure, or who abuse opioids. • The effect is mediated by histamine release and actions of nitric oxide. • The mechanisms of this effect of morphine are unclear, but suggest an alternative therapeutic target in vascular disease. AIM The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra‐arterial morphine in healthy subjects. METHODS Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine‐1 and histamine‐2 receptor blockade or during a nitric oxide clamp. RESULTS Morphine caused an increase in FBF at doses of 30 µg min−1[3.25 (0.26) ml min−1 100 ml−1][mean (SEM)] doubling at 100 µg min−1 to 5.23 (0.53) ml min−1 100 ml−1. Acute tolerance was not seen to 50 µg min−1 morphine, with increased FBF [3.96 (0.35) ml min−1 100 ml−1] (P = 0.003), throughout the 30‐min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (P = 0.008) and the nitric oxide clamp (P < 0.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1/H2 blockade was 3.06 (0.48) and 2.90 (0.17) ml min−1 100 ml−1 after 30 min, whereas with morphine alone it reached 4.3 (0.89) ml min−1 100 ml−1. CONCLUSIONS Intra‐arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine‐modulated nitric oxide release. Opioid receptor mechanisms need further exploration.
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ISSN:0306-5251
1365-2125
1365-2125
DOI:10.1111/j.1365-2125.2009.03364.x