Effect of sustained limb ischemia on norepinephrine release from skeletal muscle sympathetic nerve endings.
Acute ischemia has been reported to impair sympathetic outflow distal to the ischemic area in various organs, whereas relatively little is known about this phenomenon in skeletal muscle. We examined how acute ischemia affects norepinephrine (NE) release at skeletal muscle sympathetic nerve endings. We implanted a dialysis probe into the adductor muscle in anesthetized rabbits and measured dialysate NE levels as an index of skeletal muscle interstitial NE levels. Regional ischemia was introduced by microsphere injection and ligation of the common iliac artery. The time courses of dialysate NE levels were examined during prolonged ischemia. Ischemia induced a decrease in the dialysate NE level (from 19+/-4 to 2.0+/-0 pg/ml, mean+/-S.E.), and then a progressive increase in the dialysate NE level. The increment in the dialysate NE level was examined with local administration of desipramine (DMI, a membrane NE transport inhibitor), omega-conotoxin GVIA (CTX, an N-type Ca(2+) channel blocker), or TMB-8 (an intracellular Ca(2+) antagonist). At 4h ischemia, the increment in the dialysate NE level (vehicle group, 143+/-30 pg/ml) was suppressed by TMB-8 (25+/-5 pg/ml) but not by DMI (128+/-10 pg/ml) or CTX (122+/-18 pg/ml). At 6h ischemia, the increment in the dialysate NE level was not suppressed by the pretreatment. Ischemia induced biphasic responses in the skeletal muscle. Initial reduction of NE release may be mediated by an impairment of axonal conduction and/or NE release function, while in the later phase, the skeletal muscle ischemia-induced NE release was partly attributable to exocytosis via intracellular Ca(2+) overload rather than opening of calcium channels or carrier mediated outward transport of NE.
Kuroko
Yosuke
Y
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Tokunaga
Noriyuki
N
Yamazaki
Toji
T
Akiyama
Tsuyoshi
T
Ishino
Kozo
K
Sano
Shunji
S
Mori
Hidezo
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D003956:Dialysis; D005121:Extremities / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D009411:Nerve Endings / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000378:metabolism*
D015220:Calcium Channels; D019344:Lactic Acid; D002118:Calcium; D009638:Norepinephrine