Targeted deletion of the neutral endopeptidase gene alters
ventilatory responses to acute hypoxia in mice..
Grasemann, H., B. Lu, A. Jiao, J. Boudreau, N. P. Gerard and G. T. De
Sanctis.
1 Combined Program in Pulmonary and Critical Care Medicine, Brigham
& Women's Hospital and Harvard Medical School, 75 Francis Street,
Boston, Massachusetts 02115, USA and 2 Ina Sue Perlmutter Laboratory,
Children's Hospital, Department of Medicine, Beth Israel Deaconess
Medical Center and Harvard Medical School, 330 Brookline Ave, Boston,
MA 02215, USA
APStracts 6:0272A, 1999.
Neutral endopeptidase (NEP) is one of the major endopeptidases
responsible for the inactivation of substance P (SP) 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 (Wt) and mice in which the NEP gene was deleted (NEP -/-).
Ventilation was measured while breathing room air, 12 % O2 in N2 and
8 % O2 in N2. Deletion of the NEP gene caused marked alterations in
both the magnitude and composition of the hypoxic ventilatory
response to both 8 % O2 in N2 and 12% O2 in N2 when compared to the
Wt 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% O2 due to a
significantly greater shortening of expiratory time (TE). The results
of these studies demonstrate that NEP plays an important role in
modifying the expression of the ventilatory response to acute
hypoxia.
Received 17 February 1999; accepted in final form 8 June 1999.
APS Manuscript Number A129-9.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999