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Articles in PresS, published online ahead of print January 4, 2002
J Appl Physiol, 10.1152/jap.00688.2001
Submitted on July 5, 2001
Accepted on December 13, 2001
1 Pediatrics, Duke University Medical Center, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: chita001{at}mc.duke.edu.
We have previously shown that maturation of airway smooth muscle (ASM) contractility may play a role in the airway hyperresponsiveness displayed by juveniles of many species, including humans. ASM relaxation, which could also contribute to airway hyperresponsiveness, has neither been described nor quantified during maturation. Therefore, we studied ASM relaxation during and after electrical field stimulation (EFS) in tracheal strips from 1 week, 3 week, and 3 month old guinea pigs. Strips were stimulated (60Hz, 18V) at their optimal length for 15, 20, and 25 seconds, with and without the cyclooxygenase inhibitor indomethacin. To evaluate the role of the epithelium, de-epithelialized strips from adult animals were also studied. New indices were developed to quantify relaxation during EFS. We measured the time course of tension relaxation and its maximum rate (RTR) during the EFS, as well as the residual tension at the end of the EFS (TCTend). After EFS, we measured the maximum RTR and the time needed to reduce to half the TCTend. Relaxation during the EFS significantly increased with age. Indomethacin reduced this age-difference by increasing relaxation in strips from younger animals. By contrast, removal of the epithelium in adult strips decreased relaxation. Relaxation after EFS decreased with age and was not affected by indomethacin. In adult strips it was further reduced by epithelium removal. Our results show that during EFS 1) airway smooth muscle relaxation increases with age, 2) cyclooxygenase metabolites oppose relaxation in younger animals, 3) epithelium removal inhibits relaxation. We suggest that a reduced ASM relaxing ability during stimulation may be involved in juvenile airway hyperresponsiveness.
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