| First Author | Kuwaki T | Year | 1996 |
| Journal | Am J Physiol | Volume | 270 |
| Issue | 6 Pt 2 | Pages | R1279-86 |
| PubMed ID | 8764295 | Mgi Jnum | J:34053 |
| Mgi Id | MGI:81887 | Doi | 10.1152/ajpregu.1996.270.6.R1279 |
| Citation | Kuwaki T, et al. (1996) Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1. Am J Physiol 270(6 Pt 2):R1279-86 |
| abstractText | We studied respiratory functions in mutant mice deficient in endothelin-1 (ET-1) generated by gene targeting. In conscious adult mice heterozygous for ET-1 gene mutation (ET+/- heterozygous mice), arterial PO2 was significantly lower, PCO2 tended to be higher, and pH tended to be lower than in wild-type littermates. When these conscious mice breathed room air, respiratory minute volume and rate, determined by body plethysmography, were not significantly different between the two groups. However, when ET+/- heterozygous mice were subjected to systemic hypoxia (1:1 air-N2) or hypercapnia (5% CO2-95% O2), increases in respiratory minute volume were significantly attenuated. In conscious newborn ET-/- homozygous mice delivered by cesarean section and tracheotomized, ventilatory responses to systemic hypoxia and hypercapnia, regularly observed in newborn wild-type mice, were almost totally absent. In urethan-anesthetized adult ET+/- heterozygous mice, increases in phrenic nerve discharges in response to hypoxia and hypercapnia were significantly attenuated. Our results demonstrate that ventilatory responses to hypoxia and hypercapnia are impaired in ET-1-deficient mice and suggest that endogenous ET-1 participates in the physiological control of ventilation. |
