First Author | Grasemann H | Year | 1999 |
Journal | J Appl Physiol (1985) | Volume | 87 |
Issue | 4 | Pages | 1266-71 |
PubMed ID | 10517751 | Mgi Jnum | J:59717 |
Mgi Id | MGI:1352087 | Doi | 10.1152/jappl.1999.87.4.1266 |
Citation | Grasemann H, et al. (1999) Targeted deletion of the neutral endopeptidase gene alters ventilatory responses to acute hypoxia in mice. J Appl Physiol 87(4):1266-71 |
abstractText | Neutral endopeptidase (NEP) is one of the major endopeptidases responsible for the inactivation of substance P in the carotid body, a neurotransmitter shown to be important in the transduction of hypoxic stimuli. Ventilatory responses to acute hypoxia were measured by indirect plethysmography in unanesthetized, unrestrained wild-type mice and in mice in which the NEP gene was deleted (NEP -/-). Ventilation was measured while the animals breathed room air: 12% O(2) in N(2) and 8% O(2) in N(2). Deletion of the NEP gene caused marked alterations in both the magnitude and composition of the hypoxic ventilatory response to both 8% O(2) in N(2) and 12% O(2) in N(2), compared with the wild-type mice (C57BL/6J) on the same genetic background as the NEP -/- mice. Treatment of C57BL/6J mice with thiorphan, a NEP inhibitor, resulted in a greater ventilatory response to 8% O(2) because of a significantly greater shortening of expiratory time. The results of these studies demonstrate that NEP plays an important role in modifying the expression of the ventilatory response to acute hypoxia. |