| First Author | Nagase T | Year | 1999 |
| Journal | J Appl Physiol (1985) | Volume | 87 |
| Issue | 6 | Pages | 2020-4 |
| PubMed ID | 10601144 | Mgi Jnum | J:59807 |
| Mgi Id | MGI:1352177 | Doi | 10.1152/jappl.1999.87.6.2020 |
| Citation | Nagase T, et al. (1999) Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice. J Appl Physiol 87(6):2020-4 |
| abstractText | Endothelin (ET)-1 has been shown to have various pathophysiological roles in the lung. Recently, it has been reported that ET-1 and a gene encoding ET-1 (Edn1) might be involved in airway hyperresponsiveness, which is a major feature of bronchial asthma. Meanwhile, it remains unclear whether ET-1 might be involved in airway remodeling in vivo. In the present study, we hypothesized whether ET-1 might play a role in airway remodeling, leading to altered responsiveness. To test this hypothesis, we investigated airway function in vivo and airway wall structure in Edn1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and Edn1(+/+) wild-type mice. In the physiological study, enhanced responses in lung elastance and resistance to methacholine administration were observed in Edn1(+/-) mice, whereas there was no difference in serotonin responsiveness. In the morphometric study, there were no differences in either lamina propria or airway smooth muscle thickness between Edn1(+/-) mice and Edn1(+/+) mice. These findings suggest that ET-1 gene disruption is involved in methacholine pulmonary hyperresponsiveness via functional mechanism, but not airway remodeling, in mice. The ET-1 knockout mice may provide appropriate models to study diseases related to ET-1 metabolism. |
