Abstract
Ischemia, reperfusion, and subsequent free radical damage have been implicated in many voiding disorders. Our goal was to investigate further the mechanisms of these disorders, with particular emphasis on nerve and mitochondrial function and on detrusor smooth-muscle cells. The effects on contractile responses to various stimulations, citrate synthase, choline acetyltransferase activities, and vesicular acetylcholine transporter were evaluated after ischemia alone and ischemia/reperfusion 2 h, 7 days, and 14 days. Nerve density and detrusor cell apoptosis were also measured. The contractile responses were significantly decreased at both 7 and 14 days reperfusion, although at 14 days some recovery was observed. Similar patterns were seen for the intramural nerves, both nerve cell cytoskeletal structures and cholinergic neurotransmitters. Citrate synthase activity was also depressed by ischemia and 2 h reperfusion, but the activity recovered by 7 days. Detrusor cell apoptosis was not significantly affected by ischemia and 2 h reperfusion; but showed an approximately 14-fold increase at both 7 and 14 days reperfusion. Reperfusion following ischemia resulted in worsening intramural bladder nerve dysfunction, nerve fiber injury, mitochondrial injury, and damaged detrusor muscle cells. However, at 14 days reperfusion, nerve and mitochondrial regeneration occurred and resulted in partial recovery of contractile function.
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Abbreviations
- I/R:
-
Ischemia and reperfusion
- ROS:
-
Reactive oxygen species
- RNS:
-
Reactive nitrogen species
- NO:
-
Nitric oxide
- ATP:
-
Adenosine triphosphate
- VAChT:
-
Vesicular acetylcholine transporter
- ChAT:
-
Choline acetyltransferase
- CS:
-
Citrate synthase
- FS:
-
Field stimulation
- SOD:
-
Superoxide dismutase
- DTNB:
-
5,5′-Dithiobis-2-nitrobenzoic acid
- TdT:
-
Terminal deoxynucleotidyl transferase
- TUNEL:
-
Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling
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Acknowledgements
This material is based upon work supported in part by the Office of Research and Development Medical Research Service, Department of Veteran’s Affairs. And in part by NIH grant RO-1-DK 067114 and the Capital Region Medical Research Foundation.
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Juan, YS., Chuang, S.M., Kogan, B.A. et al. Effect of ischemia/reperfusion on bladder nerve and detrusor cell damage. Int Urol Nephrol 41, 513–521 (2009). https://doi.org/10.1007/s11255-008-9492-y
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DOI: https://doi.org/10.1007/s11255-008-9492-y