Effect of oxidant challenge on contractile function of the aging
rat diaphragm.
Lawler, John M., Camala C. Cline, Zhe Hu, and J. Richard Coast.
Respiratory Muscle Laboratory, Eloise Beard Smith Human Performance
Laboratories, Dept. of Health and Kinesiology, Texas A&M
University, College Station, TX 77843-4243
APStracts 3:0206E, 1996.
Although controversial, there is growing evidence that reactive oxygen
species (ROS) alter contractions of skeletal muscle, including the
diaphragm. However, the impact of ROS on contractility of the aging
diaphragm is unknown. The xanthine oxidase (0.01 U x ml-1) system was
used as a ROS generator, imposing an oxidant challenge. Contractile
function (twitch tension; twitch time-to-peak tension; twitch one
-half relaxation time; tension at 10 and 20 Hz; maximal tetanic
tension at 100 Hz) of costal diaphragm fiber bundles from young (4
mo) and old (25 mo) Fischer-344 rats was examined in vitro before
(PRE) and after treatment with control Krebs solution (YC & OC),
or with xanthine oxidase (0.01 U x ml-1) + hypoxanthine (0.29 mg x
ml-1) substrate (YXO & OXO). Contractile function of fiber
bundles were re-assessed following oxidant challenge in an unfatigued
state (POST-u), or 10 minutes following a fatiguing stimulation
protocol (POST-f). Oxidant challenge in the unfatigued fiber bundles
increased twitch tension and tension at 10 and 20 Hz in YXO, but not
OXO, without increasing maximal tetanic tension (Po). Conversely,
xanthine oxidase significantly depressed fatigued diaphragm twitch
and low frequency tension in both OXO and YXO, when compared to
controls. Po was depressed POST-f in OXO but not YXO. Oxidant
challenge also increased twitch one-half relaxation time of the
fatigued diaphragm in both age groups Further, fiber bundles from old
rats suffered greater fatigue during the stimulation protocol. We
conclude that the response to oxidant challenge and increased
contractile demand is impaired in the aging diaphragm.
Received 9 April 1996; accepted in final form 12 September 1996.
APS Manuscript Number E179-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996