Attenuation of rat diaphragm low-frequency fatigue by vanadate in vitro.
Sodium vanadate inhibits protein tyrosine phosphatases, including in skeletal muscle. Vanadate increases contractile force of airway, vascular and gastrointestinal smooth muscle. The present study tested the hypothesis that vanadate augments skeletal muscle contractility. Rat diaphragm muscle strips (n=26 from 12 animals) were studied in vitro at 37 degrees C. Muscles contracted isometrically while stimulated supramaximally with one of two protocols: 30 min of continuous 0.1 Hz stimulation, or 5 min of intermittent 20 Hz stimulation (duty cycle 0.33). Vanadate (500 microM)-treated muscle strips were compared with untreated muscle. Vanadate did not affect force or isometric twitch kinetics of otherwise quiescent muscle. During prolonged 0.1 Hz stimulation, force of control muscles declined by 17 +/- 4% over 30 min, whereas muscles incubated with vanadate maintained force virtually unchanged. Force over time was significantly greater with than without vanadate (P = 0.03), with values being significantly different during the last 10 min of the 30 min stimulation period. In the absence of vanadate force declined at a rate of approximately 0.6% per min, whereas with vanadate the rate of force decline was less than 0.1% per min (P < 0.02). During intermittent 20 Hz stimulation, the degree of force decline was not affected by vanadate at any time over a course of 5 min. Isometric contractile kinetics were not altered by vanadate during either 0.1 or 20 Hz stimulation. These data suggest that vanadate ameliorates low- but not higher-frequency fatigue in diaphragm, suggesting a role for protein tyrosine phosphorylation in the regulation of muscle fatigue resistance.
van Lunteren
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Case Western Reserve University, Cleveland, OH 44106, USA. exv4@po.cwru.edu
Snajdar
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D000818:Animals; D003964:Diaphragm / Q000187:drug effects*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases