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In vitro Measurements of Tracheal Constriction Using Mice
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In vitro Measurements of Tracheal Constriction Using Mice

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Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid

Lu Wang1, Valeria Pozzato, Graziella Turato

  • 1Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|March 11, 2008
PubMed

Insights

Infant guinea pig airway smooth muscle shows less relaxation due to higher prostanoid release. Cyclooxygenase-2 inhibition improves relaxation, suggesting prostanoids regulate airway function in young animals.

Area of Science:

  • Pulmonary Physiology
  • Pharmacology
  • Developmental Biology

Background:

  • Infant airway smooth muscle (ASM) exhibits reduced spontaneous relaxation compared to adult ASM.
  • Prostanoids, produced by cyclooxygenase (COX), are implicated in this age-related difference.
  • The specific roles of leukotrienes and COX isoforms in infant ASM relaxation require further investigation.

Purpose of the Study:

  • To determine if leukotrienes contribute to reduced spontaneous relaxation in infant ASM.
  • To investigate the differential roles of COX-1 and COX-2 in regulating ASM relaxation.
  • To examine the developmental regulation of prostanoid release in guinea pig ASM.

Main Methods:

  • Tracheal strips from different age groups of guinea pigs were used to measure relaxation.
  • Prostanoid release was quantified from tracheal segments.
  • Pharmacological agents including lipoxygenase inhibitor, cysteinyl leukotriene receptor-1 antagonist, COX-1 inhibitor, and COX-2 inhibitor were employed.

Main Results:

  • Inhibition of lipoxygenase or leukotriene receptor antagonism did not alter spontaneous relaxation.
  • Inhibition of COX-2, but not COX-1, significantly enhanced spontaneous relaxation.
  • Basal prostanoid release was higher in infant ASM and decreased with age, with thromboxane B2 being the predominant metabolite.

Conclusions:

  • Leukotrienes do not play a role in the reduced spontaneous relaxation of infant ASM.
  • COX-2-derived prostanoids contribute to diminished ASM relaxation in immature guinea pigs.
  • Elevated prostanoid levels in infant ASM may influence airway hyperresponsiveness in young animals.

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