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Mutant mice deficient in NOS‐1 exhibit attenuated long‐term facilitation and short‐term potentiation in breathing
Author(s) -
Kline David D.,
Overholt Jeffery L.,
Prabhakar Nanduri R.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.014571
Subject(s) - nitric oxide , nitric oxide synthase , respiration , ventilation (architecture) , long term potentiation , hypoxia (environmental) , medicine , endocrinology , respiratory system , chemistry , wild type , mutant , oxygen , biology , biochemistry , anatomy , mechanical engineering , receptor , organic chemistry , engineering , gene
The objective of the present study is to examine the potential role of nitric oxide (NO) in short‐term potentiation (STP) and long‐term facilitation (LTF) of breathing. Experiments were performed in wild‐type (WT) and mutant mice deficient in nitric oxide synthase‐1 (NOS‐1), as well as in WT mice administered the NOS‐1 inhibitor 7‐nitroindazole (7‐NI; 50 mg kg −1 ; i.p. ). Respiratory responses following either single or recurrent episodes of hypoxia (7 % O 2 , balance N 2 ) were analysed in unanaesthetised animals by body plethysmography along with rate of O 2 consumption (V̇ O2 ) and CO 2 production (V̇ CO2 ). After a single hypoxic challenge, respiration in WT mice remained elevated for 5 min, suggesting STP in ventilation. Following termination of three consecutive hypoxic challenges, respiration remained elevated during normoxia for as long as 30 min, indicating LTF in breathing under awake conditions. STP and LTF were significantly attenuated or absent in WT mice after 7‐NI. A similar attenuation or absence of STP and LTF was also seen in NOS‐1 mutant mice. Changes in V̇ O2 and V̇ CO2 were comparable among mice during the post‐hypoxic period, suggesting that the absence of STP and LTF was not due to alterations in body metabolism. These results suggest endogenous NO is an important physiological modulator of ventilatory STP and LTF.