Abstract
This study was designed to test the hypotheses that furosemide directly causes relaxation in human fetal airway and that delivery of loop diuretics to either the adventitial or epithelial surface of newborn mouse airway results in equivalent relaxation. Isometric tension changes were measured in human fetal (11–16 wk) trachea and mainstem bronchus rings exposed to furosemide (300 μM) or saline after acetylcholine or leukotriene D4 constriction. Significant decreases in isometric tension to furosemide were demonstrated after constriction with acetylcholine or leukotriene D4. To examine the site of effect and mimic aerosolized and systemic administration, furosemide (3–300 μM) and bumetanide (0.3–30 μM) were applied separately to epithelial and adventitial surfaces of newborn mouse airways. No differences in airway diameter changes to epithelial or adventitial furosemide or bumetanide were observed, but a 10-fold difference in potency was found. In summary, human fetal airway relaxed to furosemide when constricted with either neurotransmitter or inflammatory mediator in vitro. Further, no differences in relaxation to equimolar epithelial and adventitial furosemide were observed in isolated newborn mouse airway. Taken together, this provides evidence that furosemide has a direct, nonepithelial-dependent effect on airway smooth muscle tone.
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Abbreviations
- LTD4:
-
leukotriene D4
- EC50:
-
effective concentration to produce 50% of maximal response
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Acknowledgements
The authors thank Drs. David Easa and John Claybaugh for their advcice and Naomi Fujiwara and Asoka DeSilva for their technical support. Human tissue used for this research was obtained from the Central Laboratory for Human Embryology, University of Washington, supported by National Institutes of Health Grant HD 00836 to Dr. Alan Fantel.
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The opinions or assertions contained herein are the private views of the authors and are not to be considered as official or as reflecting the views of the Department of the Army or the Department of Defense.
Supported by Kapi'olani Health Research Institute, the US Army Health Service Command, a Leahi Fund Grant of the Hawai'i Community Foundation, and Research Centers in Minority Institutions awards, U54 RR14607 and P20 RR11091, from the National Center for Research Resources, NIH.
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Iwamoto, L., Gries, D. & Nakamura, K. Loop Diuretics and In Vitro Relaxation of Human Fetal and Newborn Mouse Airways. Pediatr Res 50, 273–276 (2001). https://doi.org/10.1203/00006450-200108000-00018
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DOI: https://doi.org/10.1203/00006450-200108000-00018
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