Submitted on September 26, 2007
Accepted on March 3, 2008
Reduced Spontaneous Relaxation in Immature Guinea Pig Airway Smooth Muscle is Associated with Increased Prostanoid Release
Lu Wang1, Valeria Pozzato1, Graziella Turato2, Aasakiran Madamanchi1, Thomas M. Murphy3, and Pasquale Chitano4*
1 Pediatrics, Duke University Medical Center, Durham, North Carolina, United States
2 Scienze Cardiologiche, Universita degli Studi di Padova, Padova, Italy
3 Department of Pediatrics, Division of Pulmonary Diseases, Duke University Medical Center, Durham, North Carolina, United States
4 Pediatrics / Pulmonary Diseases, Duke University Medical Center, Durham, North Carolina, United States
* To whom correspondence should be addressed. E-mail: chita001{at}mc.duke.edu.
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 abolished 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, COX1 and COX2, differentially regulate spontaneous relaxation; 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 COX1 inhibitor, or a COX2 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 COX2, but not COX1, 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 to older animals. By regulating ASM relaxation prostanoids may play a role in the airway hyperresponsiveness at young age.
