Effect of Modulation of Nitric Oxide on Rat Diaphragm Isometric Contraction and Fatigue Resistance in Hyperoxic and Hypoxic Conditions | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 10, Volume 27, Issue 2, December 2007, Pages 135-156 PDF (224.84 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2007.37313 | ||
| Authors | ||
| Sandra Younan* 1; Amani Ali2 | ||
| 1The Department of Physiology, Faculty of Medicine, Cairo Universitiy | ||
| 2The Department of Physiology, Faculty of Medicine,El-Fayoum University | ||
| Abstract | ||
| The role of nitric oxide (NO) in ventillatory muscle contractile function has been under debate for several years. Moreover little is known about NO role under hypoxic conditions and the contribution of inducible nitric oxide synthetase (iNOS) in its generation. The aim of this study was to investigate the effect of NO on the force generation and fatigue resistance of the rat diaphragm muscle under acute in vitro hypoxia and to compare these effects to those under hyperoxic conditions. The effects of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA), the NO scavenger hemoglobin, and the NO donor Na nitroprusside on the maximal twitch force (Ft), submaximal tetanic force (F30), maximal tetanic force (F0) and isotonic endurance time under hyperoxic and hypoxic conditions were evaluated. Also diaphragm iNOS activity and nitrotyrosine level as a marker of peroxynitrite were measured. Inhibition of NO production and its scavenging using L-NMMA and Hb respectively had no effect on the diaphragm isometric contraction, the recruitment of its muscle fibers and fatigue resistance under hyperoxic condition. Hypoxia significantly reduced Ft, F30 , F0 and fatigue resistance with increased diaphragm iNOS activity and nitrotyrosine level. Hypoxia significantly reduced Ft and F0 in L-NMMA group compared to hyperoxic control one. While L-NMMA significantly increased F30 and decreased isotonic fatigability during hypoxia concomitant with reduction of iNOS activity and nitrotyrosine level compared to hypoxic control group. Moreover Hb induced similar results with additional significant improvement of Ft and F0. The effects of L-NMMA were prevented by co-administration with the NOS substrate L-arginine. On the other hand, Excessive exogenous NO production by Nanitroprusside markedly decreased isometric contractile and fatigue properties during both hyperoxia and hypoxia. In conclusion the results of this study showed that the iNOS is activated in the diaphragm under hypoxia and may contribute partially to NO generation in hypoxia. Also they indicate that NO has a more prominent role in rat diaphragm under in vitro hypoxia compared to hyperoxic condition and that it contributes to the depression of force generation in the hypoxic diaphragm in vitro. Inhibition of NO generation during hypoxia may have a protective effect which could be a target in clinical conditions. | ||
| Keywords | ||
| NO; Diaphragm; iNOS; Fatigue | ||
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