Mutant mice deficient in NOS-1 exhibit attenuated long-term facilitation and short-term potentiation in breathing.
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 x kg(-1); I.P.). Respiratory responses following either single or recurrent episodes of hypoxia (7% O2, balance N2) were analysed in unanaesthetised animals by body plethysmography along with rate of O2 consumption (VO2)) and CO2 production (VCO2). 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 VO2 and VCO2 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.
Kline
David D
DD
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.
Overholt
Jeffery L
JL
Prabhakar
Nanduri R
NR
D000818:Animals; D002245:Carbon Dioxide; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D010101:Oxygen Consumption; D012016:Reference Values; D012119:Respiration
D004791:Enzyme Inhibitors; D007191:Indazoles; D002245:Carbon Dioxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C080122:7-nitroindazole