EFFECT OF OXIDANT CHALLENGE ON CONTRACTILE FUNCTION OF THE AGING RAT DIAPHRAGM

Although controversial, growing evidence indicates that reactive oxyge n species (ROS) alter contractions of skeletal muscle, including the d iaphragm. However, the impact of ROS on contractility of the aging dia phragm is unknown. The xanthine oxidase (0.01 U/ml) system was used as an ROS generator, imposing an oxidant challenge. Contractile function [twitch tension; twitch time to peak tension; twitch one-half relaxat ion time; tension at 10 and 20 Hz; maximal tetanic tension (P-o) at 10 0 Hz] of costal diaphragm fiber bundles from young (4 mo) and old (25 mo) Fischer 344 rats was examined in vitro before and after treatment with control Krebs solution [young control (YC) and old control (OC)], or with xanthine oxidase (XO; 0.01 U/ml) plus hypoxanthine (0.29 mg/m l) substrate [young XO treated (YXO) and old XO treated (OXO)]. Contra ctile function of fiber bundles was reassessed after oxidant challenge in an unfatigued state (Post-u) or 10 min after a fatiguing stimulati on protocol (Post-f). Oxidant challenge in the unfatigued fiber bundle s increased twitch tension and tension at 10 and 20 Hz in YXO, but not OXO, without increasing P-o. Conversely, XO significantly depressed f atigued diaphragm twitch and low-frequency tension in both OXO and YXO , compared with controls. P-o was depressed Post-f in OXO but not YXO. Oxidant challenge also increased twitch one-half relaxation time of t he fatigued diaphragm in both age groups. Furthermore, fiber bundles f rom old rats suffered greater fatigue during the stimulation protocol. We conclude that the response to oxidant challenge and increased cont ractile demand is impaired in the aging diaphragm.