Superoxide scavengers augment contractile but not energetic responses to hypoxia in rat diaphragm

Abstract

Acute exposure to severe hypoxia depresses contractile function and induces adaptations in skeletal muscle that are only partially understood. Previous studies have demonstrated that antioxidants (AOXs) given during hypoxia partially protect contractile function, but this has not been a universal finding. This study confirms that specific AOXs, known to act primarily as superoxide scavengers, protect contractile function in severe hypoxia. Furthermore, the hypothesis is tested that the mechanism of protection involves preservation of high-energy phosphates (ATP, creatine phosphate) and reductions of P(i). Rat diaphragm muscle strips were treated with AOXs and subjected to 30 min of hypoxia. Contractile function was examined by using twitch and tetanic stimulations and the degree of elevation in passive force occurring during hypoxia (contracture). High-energy phosphates were measured at the end of 30-min hypoxia exposure. Treatment with the superoxide scavengers 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron, 10 mM) or Mn(III)tetrakis(1-methyl-4-pyridyl) porphyrin pentachloride (50 microM) suppressed contracture during hypoxia and protected maximum tetanic force. N-acetylcysteine (10 or 18 mM) had no influence on tetanic force production. Contracture during hypoxia without AOXs was also shown to be dependent on the extracellular Ca(2+) concentration. Although hypoxia resulted in only small reductions in ATP concentration, creatine phosphate concentration was decreased to approximately 10% of control. There were no consistent influences of the AOX treatments on high-energy phosphates during hypoxia. The results demonstrate that superoxide scavengers can protect contractile function and reduce contracture in hypoxia through a mechanism that does not involve preservation of high-energy phosphates.

Effects of sustained hypoxia on sternohyoid and diaphragm muscle during development

“…Superoxide scavengers have been shown to protect diaphragm maximum tetanic force in hypoxia in vitro [58]. Furthermore, tempol was effective in the protection of superoxide-induced impairment in tetanic force and maximum calcium-activated force due to heat stress [59] Initial Normoxia SH [21][22][23][24][25][26][27][28] Specific force N .…”

Structural and Functional Properties of an Upper Airway Dilator Muscle in Aged Obese Male Rats

“…Since ROS are implicated in skeletal muscle function and antioxidants have been shown to improve skeletal muscle performance [17,18] including diaphragm [19] and pharyngeal dilator [20] muscle function, we sought to test the effects of an antioxidant on sternohyoid muscle performance in aged obese rats. Our results are consistent with and extend our previous findings in young lean airway muscle [20].…”

Maternal creatine supplementation from mid-pregnancy protects the newborn spiny mouse diaphragm from intrapartum hypoxia-induced damage

“…There is an increased reliance on anaerobic pathways (5), which, when prolonged, results in an accumulation of metabolic byproducts and ionic disturbances linked with muscle fatigue (6). Excessive production of reactive oxygen species occurs and promotes myosin and actin degradation (7), leading to damage of myofibrillar proteins (8) and reduced functional capacity of skeletal muscles (9).…”