title: Nitric oxide production in the ventilatory muscles in response to acute resistive loading.
abstract: The effect of muscle activation on muscle nitric oxide (NO) production remains controversial. Whereas NO release increases in in vitro activated muscles and in vivo limb muscles, diaphragmatic NO synthase (NOS) activity declines after 3 h of inspiratory resistive loading (IRL). We tested in this study the hypotheses that acute IRL decreases diaphragmatic NO derivatives levels and reduces protein expression of neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) NO synthases, as well as 3-nitrotyrosine formation. Anesthetized, tracheostomized, spontaneously breathing adult rats were subjected to IRL (50% of the maximum inspiratory pressure) for 1, 3, or 6 h. Quietly breathing rats served as controls. After 3 h of IRL, muscle eNOS and nNOS protein levels rose by 80 and 60% of control values, respectively. Whereas eNOS expression did not change any further, nNOS expression reached 550% of control values after 6 h of IRL. Strong iNOS protein expression was detected in the diaphragms after 6 h of IRL. Total NO derivatives levels in the diaphragm declined during IRL as a result of reduction in nitrate, nitrite, and nitrosothiols. Diaphragmatic protein tyrosine nitration decreased in response to IRL, and this reduction was mainly due to reduced tyrosine nitration of enolase and aldolase. We conclude that diaphragmatic NO derivatives levels decline in response to IRL and that the rise in diaphragmatic NOS protein expression may be a compensatory response designed to counterbalance the decline in NOS activity.
authors.affiliation: Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
authors.forename: Karuthapillai
authors.initials: K
authors.lastname: Govindaraju
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Parthenis
authors.forename: David H
authors.initials: DH
authors.lastname: Eidelman
authors.forename: Yasu
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Sabah N A
authors.initials: SN
authors.lastname: Hussain
mesh_terms: D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D056445:Cytoplasmic Dyneins; D003964:Diaphragm / Q000378:metabolism*; D004398:Dyneins / Q000096:biosynthesis; D016232:Endothelins / Q000096:biosynthesis; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D016232:Endothelins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D052250:Nitric Oxide Synthase Type III; C486069:Dynll1 protein, rat; D056445:Cytoplasmic Dyneins; D004398:Dyneins