| First Author | Nagase T | Year | 1998 |
| Journal | Am J Respir Crit Care Med | Volume | 157 |
| Issue | 2 | Pages | 560-4 |
| PubMed ID | 9476873 | Mgi Jnum | J:46299 |
| Mgi Id | MGI:1197537 | Doi | 10.1164/ajrccm.157.2.9706009 |
| Citation | Nagase T, et al. (1998) Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1. Am J Respir Crit Care Med 157(2):560-4 |
| abstractText | Endothelin-1 (ET-1) has recently been reported to have a potential pathophysiologic role in bronchial asthma. In the current study, we hypothesized whether ET-1 and a gene encoding ET-1 might be involved in airway hyperresponsiveness (AHR), which is a major feature of bronchial asthma. To test this hypothesis, we investigated airway responsiveness in ET-1(+/-)heterozygous knockout mice, which genetically produce lower levels of ET-1, and in ET-1(+/+) wild-type mice. Airway responsiveness was assessed through the concentration of an agonist required to double lung resistance (EC200 RL). Unexpectedly, airway responsiveness to methacholine was markedly enhanced in ET- 1(+/-)heterozygous mice as compared with ET-1(+/+) wild- type mice (EC200RL:1.8 +/- 0.1 versus 21.6 +/- 5.6 mg/ml, p < 0.002), Pretreatment with the nitric oxide (NO) synthase inhibitor N-g-monomethyl-L-arginine (L-NMMA) significantly enhanced methacholine responsiveness in ET- 1(+/+) wild-type mice, but not in ET-1(+/-)heterozygous mice. Meanwhile, there was no difference between ET-1(+/- )heterozygous mice and the wild-type mice in airway responsiveness to 5-hydroxytryptamine (5-HT). In sensitized mice, no significant differences in responsiveness to antigen were observed between the two groups. These findings suggest that the gene encoding ET-1 may be potentially involved in the etiology of airway hyperreactivity, and that the decrease in ET-1 concentration is associated with AHR to methacholine. In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology. |
