Kuwaki T, Cao W H, Kurihara Y, Kurihara H, Ling G Y, Onodera M, Ju K H, Yazaki Y, Kumada M
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Am J Physiol. 1996 Jun;270(6 Pt 2):R1279-86. doi: 10.1152/ajpregu.1996.270.6.R1279.
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.
我们研究了通过基因靶向产生的内皮素-1（ET-1）缺陷型突变小鼠的呼吸功能。在成年ET-1基因突变杂合子（ET+/-杂合子小鼠）的清醒小鼠中，动脉血氧分压（PO2）显著降低，二氧化碳分压（PCO2）有升高趋势，pH值有降低趋势，与野生型同窝小鼠相比。当这些清醒小鼠呼吸室内空气时，通过体容积描记法测定的呼吸分钟量和呼吸频率在两组之间无显著差异。然而，当ET+/-杂合子小鼠受到全身性低氧（1:1空气-N2）或高碳酸血症（5% CO2-95% O2）刺激时，呼吸分钟量的增加显著减弱。在通过剖宫产分娩并进行气管切开的清醒新生ET-/-纯合子小鼠中，新生野生型小鼠中经常观察到的对全身性低氧和高碳酸血症的通气反应几乎完全缺失。在乌拉坦麻醉的成年ET+/-杂合子小鼠中，对低氧和高碳酸血症的膈神经放电增加显著减弱。我们的结果表明，ET-1缺陷型小鼠对低氧和高碳酸血症的通气反应受损，提示内源性ET-1参与通气的生理控制。
