title: Improved tolerance of acute severe hypoxic stress in chronic hypoxic diaphragm is nitric oxide-dependent.
abstract: The effects of chronic hypoxia (CH) on respiratory muscle performance have hardly been investigated, despite clinical relevance. Results from recent studies are indicative of unique adaptive strategies in hypoxic diaphragm. Respiratory muscle tolerance of acute severe hypoxic stress was examined in normoxic and CH diaphragm in the presence and absence of a nitric oxide (NO) synthase inhibitor. We tested the hypothesis that improved tolerance of severe hypoxic stress in CH diaphragm is NO-dependent. Wistar rats were exposed to normoxia (sea-level, n = 6) or CH (ambient pressure = 380 mmHg, n = 6) for 6 weeks. Diaphragm muscle functional properties were determined ex vivo under severe hypoxic conditions (gassed with 95%N2/5% CO2) with and without 1 mM L-N(G)-nitroarginine (L-NNA, nNOS inhibitor). Fatigue tolerance, but not force, was significantly improved in CH diaphragm (p = 0.008). CH exposure did not affect diaphragm muscle fibre oxidative capacity determined from cluster analysis of area-density plots of muscle fibre succinate dehydrogenase activity. Acute NOS inhibition reduced diaphragm peak tetanic force (p = 0.018), irrespective of gas treatment, and completely reversed improved fatigue tolerance of the CH diaphragm. We conclude that CH exposure improves fatigue tolerance during acute severe hypoxic stress in an NO-dependent manner, independent of muscle fibre oxidative capacity.
authors.affiliation: Department of Physiology, School of Medicine, Western Gateway Building, University College Cork, Western Road, Cork, Ireland, philip.lewis@umail.ucc.ie.
authors.forename: Philip
authors.initials: P
authors.lastname: Lewis
authors.forename: Clodagh
authors.initials: C
authors.lastname: McMorrow
authors.forename: Aidan
authors.initials: A
authors.lastname: Bradford
authors.forename: Ken D
authors.initials: KD
authors.lastname: O'Halloran
mesh_terms: D000208:Acute Disease; D000222:Adaptation, Physiological; D000818:Animals; D002908:Chronic Disease; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D053580:Muscle Strength; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017208:Rats, Wistar; D012720:Severity of Illness Index; D015398:Signal Transduction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013385:Succinate Dehydrogenase