Morphine is an arteriolar vasodilator in man.
OBJECTIVE
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 microg min(-1)[3.25 (0.26) ml min(-1) 100 ml(-1)][mean (SEM)] doubling at 100 microg min(-1) to 5.23 (0.53) ml min(-1) 100 ml(-1). Acute tolerance was not seen to 50 microg 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.
Medical Toxicology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
Reza
R
Afshari
Simon R J
SR
Maxwell
David J
DJ
Webb
D Nicholas
DN
Bateman
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010991:Plethysmography / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D055815:Young Adult
D014665:Vasodilator Agents; D009020:Morphine; D006632:Histamine