title: Nitric oxide modulates neuromuscular transmission during hypoxia in rat diaphragm.
abstract: Hypoxia impairs neuromuscular transmission in the rat diaphragm. In previous studies, we have shown that nitric oxide (NO) plays a role in force modulation of the diaphragm under hypoxic conditions. The role of NO, a neurotransmitter, on neurotransmission in skeletal muscle under hypoxic conditions is unknown. The effects of the NO synthase (NOS) inhibitor nomega-nitro-L-arginine (L-NNA, 1 mM) and the NO donor spermine NONOate (Sp-NO, 1 mM) were evaluated on neurotransmission failure during nonfatiguing and fatiguing contractions of the rat diaphragm under hypoxic (PO2 approximately 5.8 kPa) and hyperoxic conditions (PO2 approximately 64.0 kPa). Hypoxia impaired force generated by both muscle stimulation at 40 HZ (P40M) and by nerve stimulation at 40 HZ (P40N). The effect of hypoxia in the latter was more pronounced. L-NNA increased P40N whereas Sp-NO decreased P40N during hypoxia. In contrast, neither L-NNA nor Sp-NO affected P40N during hyperoxia. L-NNA only slightly reduced neurotransmission failure during fatiguing contractions under hyperoxic conditions. Consequently, neurotransmission failure assessed by comparing force loss during repetitive nerve simulation and superimposed direct muscle stimulation was more pronounced in hypoxia, which was alleviated by L-NNA and aggravated by Sp-NO. These data provide insight in the underlying mechanisms of hypoxia-induced neurotransmission failure. This is important as respiratory muscle failure may result from hypoxia in vivo.
authors.affiliation: Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.forename: Leo M A
authors.initials: LM
authors.lastname: Heunks
authors.forename: Leo
authors.initials: L
authors.lastname: Ennen
authors.forename: Herwin A
authors.initials: HA
authors.lastname: Machiels
authors.forename: Henricus F M
authors.initials: HF
authors.lastname: Van Der Heijden
authors.forename: P N Richard
authors.initials: PN
authors.lastname: Dekhuijzen
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D018763:Muscle Fatigue; D020511:Neuromuscular Junction Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D019335:Nitroarginine; D013096:Spermine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase