The effect of repeated sublethal ischemia on NO/cGMP signal transduction system in gray matter of the rabbit spinal cord.
BACKGROUND
The activation of the soluble guanylate cyclase and the production of cyclic 3',5'-guanosine monophosphate (cGMP) have been reported as the primary cellular response to nitric oxide (NO) in the nervous system. Previous results indicated, that three-fold sublethal ischemia repeated at 1-h intervals induces damage in gray matter of the spinal cord. However, little is known about the changes of NO/cGMP signal transduction system in gray matter of the spinal cord under conditions of repeated sublethal ischemia.


OBJECTIVE
The aim of this study was to compare the catalytic NOS activity and cGMP concentration in the gray matter regions of lumbosacral spinal cord segments (dorsal horn, zona intermedia, ventral horn) after three (8-, 8-, 9-min) sublethal occlusions repeated at 1-h intervals.


METHODS
Twenty male rabbits, weighing 2.5-3.5 kg were used in the experiments. They were divided into two experimental groups: (1) control animals (n = 10); (2) animals subjected to three brief (8-, 8-, 9-min) occlusions, each time repeated by reperfusion lasting for 1 h (n = 10). Ischemia of lumbosacral segments was induced by ligation of the abdominal aorta just below the left renal artery (DeGirolami and Zivin, 1982). The catalytic NOS activity was determined by conversion of [3H]-L-arginine to [3H]-L-citrulline according to the method of Bredt and Snyder (1990) slightly modified by Strosznajder and Chalimoniuk (1996). cGMP concentration was assessed by radioimmunoassay method (RIA).


RESULTS
Repeated sublethal ischemia evoked a slight increase in catalytic NOS activity over control values in all gray matter regions. On the other hand, cGMP concentration in gray matter regions has a decreasing character, in a descending order: dorsal horn > zona intermedia > ventral horn. A significant impairment of NO-cGMP signal transduction was detected in the intermediate zone and ventral horns.


CONCLUSIONS
Our results indicate that threefold (8-, 8-, 9-min) sublethal ischemia repeated in 1 h intervals of reperfusion causes the impairment of NO/cGMP signal transduction system in gray matter of lumbosacral spinal cord segments and the extent of impairment is region-specific. This finding correlates with the neurological hindlimbs impairment in experimental animals. (Tab. 1, Fig. 2, Ref. 39.)
Pavel
J
J
Institute of Neurobiology, Slovak Academy of Sciences, Kosice, Slovakia. pavel@saske.sk
Lukacova
N
N
Marsala
J
J
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008159:Lumbar Vertebrae; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011817:Rabbits; D015424:Reperfusion; D015398:Signal Transduction; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism*
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP