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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
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Published on: October 19, 2013

Superoxide differentially controls pulmonary and systemic vascular tone through multiple signalling pathways.

Vladimir A Snetkov1, Sergey V Smirnov, Justin Kua

  • 1Division of Asthma, Allergy and Lung Biology, School of Medicine, King's College London, Room 3.20, Franklin Wilkins Building, Stamford Street, London SE1 9NH, UK.

Cardiovascular Research
|September 1, 2010
PubMed
Summary

Superoxide causes pulmonary artery constriction via Rho-kinase-dependent calcium sensitization and mesenteric artery relaxation by opening K(V) channels. These distinct actions highlight differential regulation of vascular tone by superoxide.

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Area of Science:

  • Vascular Physiology
  • Cardiovascular Research
  • Smooth Muscle Biology

Background:

  • Superoxide anion plays a complex role in regulating vascular tone.
  • Understanding the mechanisms underlying superoxide's constrictor and relaxant effects is crucial for cardiovascular health.

Purpose of the Study:

  • To investigate the roles of calcium (Ca2+) sensitization, ion channels, and intracellular calcium ([Ca2+]i) in mediating superoxide's effects on systemic and pulmonary arteries.
  • To differentiate the mechanisms of superoxide-induced constriction and relaxation in different vascular beds.

Main Methods:

  • Rat pulmonary and mesenteric arteries were used to study the effects of superoxide generated by 6-anilino-5,8-quinolinequinone (LY83583).
  • Vascular tension, Rho-kinase activity (assessed by MYPT-1 phosphorylation), myosin light chain phosphorylation, and intracellular calcium ([Ca2+]i) were measured.
  • Electrophysiological techniques were used to assess K(V) channel activity.

Main Results:

  • Superoxide induced constriction in pulmonary arteries and relaxation in mesenteric arteries, effects inhibited by superoxide dismutase and catalase.
  • Pulmonary artery constriction was Rho-kinase-dependent, involving increased MYPT-1 and 20 kDa myosin light chain phosphorylation, and elevated [Ca2+]i.
  • Mesenteric artery relaxation was associated with decreased [Ca2+]i and K(V) channel opening, while pulmonary artery smooth muscle cells showed K(V) current hyperpolarization.

Conclusions:

  • Superoxide induces Rho-kinase-dependent Ca2+ sensitization leading to constriction in pulmonary arteries.
  • Superoxide opens K(V) channels in both pulmonary and mesenteric arteries, but this only results in relaxation in mesenteric arteries.
  • The differential effects of superoxide on vascular tone are mediated by distinct signaling pathways involving Ca2+ sensitization and ion channel activity.