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High-dose morphine impairs vascular endothelial function by increased production of superoxide anions

Chen-Fuh Lam1, Yen-Chin Liu, Fan-Ling Tseng

  • 1Department of Anesthesiology, National Cheng Kung University Medical College and Hospital, Tainan City, Taiwan.

Anesthesiology
|February 28, 2007
PubMed
Abstract

Insights

High-dose morphine impairs vascular endothelial function by increasing oxidative stress and reducing nitric oxide activity. This study reveals a potential mechanism for morphine-induced vascular dysfunction.

Area of Science:

  • Pharmacology
  • Cardiovascular Biology
  • Oxidative Stress Research

Background:

  • The impact of high-dose morphine on vascular endothelial function remains largely unexplored.
  • A pro-oxidant effect of high-dose morphine is hypothesized to impair endothelial function.

Purpose of the Study:

  • To investigate the effects of high-dose morphine on vascular endothelial function in mice.
  • To elucidate the role of oxidative stress and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in morphine-induced vascular impairment.

Main Methods:

  • Mice received daily intraperitoneal injections of placebo or high-dose morphine (20 mg/kg) for 14 days.
  • Vasomotor function was assessed using isometric force recordings in isolated aortas.
  • Protein expression of p47phox, a subunit of NADPH oxidase, was quantified via Western blotting.
  • Superoxide anion generation was visualized using confocal microscopy and dihydroethidium staining.

Main Results:

  • High-dose morphine significantly enhanced aortic contraction responses to phenylephrine.
  • Endothelium-dependent relaxations to acetylcholine were markedly reduced in morphine-treated mice.
  • Superoxide scavenging normalized the impaired endothelial relaxations.
  • Increased dihydroethidium fluorescence and elevated p47phox levels indicated heightened oxidative stress in aortas from morphine-treated mice.
  • Morphine exposure increased reactive oxygen species production in cultured endothelial cells.

Conclusions:

  • High-dose morphine impairs vascular endothelial function by attenuating the bioavailability of endothelium-derived nitric oxide.
  • The generation of superoxide anions by NADPH oxidases appears to be a key molecular mechanism responsible for nitric oxide inactivation following high-dose morphine treatment.

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