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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/L964    most recent 00401.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, L. Articles by Chitano, P. PubMed PubMed Citation Articles by Wang, L. Articles by Chitano, P.

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

¹Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; and ²Divisione di Pneumologia, Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari, Università degli Studi di Padova, Padova, Italy

Submitted 26 September 2007 ; accepted in final form 3 March 2008

Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B₂ was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.

airway hyperresponsiveness; bronchospasm removal; cyclooxygenase; lipoxygenase; ontogenesis