Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia.
Hypoxia disturbs Ca(2+) regulation and increases the intracellular Ca(2+) concentration ([Ca(2+)](i)), which may in turn activate the nitric oxide synthase (NOS) regulated by [Ca(2+)](i). Since nitric oxide (NO) reduces the isometric contractility of rat diaphragm in vitro, we hypothesized that NO contributes to the impaired force generation of an hypoxic diaphragm. The effects of different concentrations of the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), the NO scavenger haemoglobin (150 micro mol.l(-1)) and the NO donor spermine NONOate (Sp-NO; 1 mmol.l(-1)) were determined on isometric contractility during hypoxia [partial pressure of oxygen, PO(2), about 7 kPa (about 54 mmHg)] and hyperoxia [ PO(2) about 83 kPa (about 639 mmHg)]. Hypoxia significantly reduced maximal twitch force ( F(t)), and submaximal tetanic force (30 Hz, F(30)) in all L-NMMA groups. A low concentration of L-NMMA (30 micromol.l(-1)) increased F(30) but a high concentration (1,000 micromol.l(-1)) reduced F(30) during hypoxia. The effects of L-NMMA on force generation were more pronounced during hypoxia compared to hyperoxia. Peak increases in F(30) and F(t) were observed at a concentration of 30 micromol.l(-1) L-NMMA during hypoxia, but with 10 micromol.l(-1) L-NMMA during hyperoxia. The same concentration of haemoglobin increased F(30) and F(t) less during hypoxia compared to hyperoxia. The Sp-NO reduced F(t), F(30) and maximal tetanic force (F(0)) during hypoxia; these effects were abolished in the presence of haemoglobin. The Sp-NO did not alter F(t), F(30) and F(0)during hyperoxia. We conclude that NO plays a more prominent role during hypoxia and that NO contributes to the depression of force generation in the hypoxic rat diaphragm in vitro. This change may be related to an elevated NO generation within the hypoxic diaphragm.
Zhu
Xiaoping
X
Department of Pulmonary Diseases, University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands.
Heunks
L M A
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Ennen
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L
Machiels
H A
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Dekhuijzen
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D000818:Animals; D003964:Diaphragm / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006454:Hemoglobins / Q000494:pharmacology; D018496:Hyperoxia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D019323:omega-N-Methylarginine; D013096:Spermine; D009569:Nitric Oxide