Effect of Edaravone on Ischemia / Reperfusion Injury in Rat Urinary Bladder – Changes in Smooth Muscle Cell Phenotype and Contractile Function

Abstract

Edaravone is a newly developed radical scaveng­ing agent that has been widely used for protec­tion against ischemia / reperfusion (I / R) injury in patients with cerebral infarction. The present study investigated the effects of edaravone on the I / R injury in rat urinary bladder. Adult male rats were divided in the four groups: groups 1–3 received 1 hour of ischemia followed by 1 hour of reperfusion with saline and with edaravone (1 and 3 mg / kg body weight), and group 4 were age-matched control rats. The in vivo ischemia was created by clamping the vesical arteries for 1 hour and reperfusion was accomplished by removing the clips and lasted for 1 hour. Edaravone or saline were administered after reperfusion for 30 min. Following reperfusion, the bladder was excised and separated. Bladder smooth muscle cell (SMC) phenotypic expression was investi­gated in the electron microscope. The number of contractile and non-contractile bladder SMC pheno­type according to the morphological criteria was counted and the ratio of non-contractile to contractile phenotype was calculated. The responses to electrical field stimulation and car­bachol were recorded. Edaravone administration resulted in the protection of the morphological changes and contractile responses to both EFS and carbachol that were affected by the agent. Our findings demonstrate that edaravone has a potentially protective effect on I / R-induced damage in the rat bladder.

Key words

phenotypic expression - bladder smooth muscle cell - ischemia-reperfusion injury

References

• 1 Watanabe T, Egawa M. Effects of an antistroke agent MCl-186 on cerebral arachidonate cascade.  J Pharmacol Exp Ther. 1994;  271 1624-1629
• 2 Nakashima M, Niwa M, Iwai T et al. Involvement of free radicals in cere­bral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat.  Free Radic Biol Med. 1999;  26 722-729
• 3 Azadzoi K M, Tarcan T, Siroky M B et al. Atherosclerosis-induced chronic ischemia causes bladder fibrosis and non-compliance in the rabbit.  J Urol. 1999;  161 1626-1635
• 4 Lin A TL, Chen M T, Yang C H et al. Blood flow of the urinary bladder. ­Effects of bladder outlet obstruction and correlation with energetic metabolism.  Neurourol Urodyn. 1995;  14 285-292
• 5 Siroky M B, Krane R J, Pontari M. Effect of bladder filling and contraction on bladder microcirculation.  Neurourol Urodyn (Suppl). 1993;  12 400
• 6 Greenland J E, Brading A F. Urinary bladder blood flow changes during the micturition cycle in a conscious pig model.  J Urol. 1996;  156 1858-1861
• 7 Bratslavsky G, Whitbeck C, Horan P et al. Effects of in vivo ischemia on contractile responses of rabbit bladder to field stimulation, carbachol, ATP, and KCl.  Pharmacology. 1999;  59 221-226
• 8 Levin R M, Levin S S, Zhao Y et al. Cellular and molecular aspects of bladder hypertrophy.  Eur Urol (Suppl). 1997;  32 15-21
• 9 Saito M, Miyagawa I. Bladder dysfunction after acute urinary retention in rats.  J Urol. 2001;  165 1745-1747
• 10 Schroder A, Kogan B A, Lieb J et al. Increased blood flow after catheterization and drainage in the chronically obstructed rabbit urinary bladder.  Urology. 2001;  58 295-300
• 11 Matsumoto S, Chichester P, Kogan B A et al. Structural and vascular ­response of normal and obstructed rabbit whole bladders to distension.  Urology. 2003;  62 1129-1133
• 12 Bratslavsky G, Kogan B A, Matsumoto S et al. Reperfusion injury of the rat bladder is worse than ischemia.  J Urol. 2003;  170 2086-2090
• 13 Mosse P R, Campbell G R, Wang Z L et al. Smooth muscle phenotypic expression in human carotid arteries.  Lab Invest. 1985;  53 556-562
• 14 Minhaz U, Tanaka M, Tsukamoto H et al. Effect of MCI-186 on post­ischemic reperfusion injury in isolated rat heart.  Free Radic Res. 1996;  24 361-367
• 15 Okatani Y, Wakatsuki A, Enzan H et al. Edaravone protects against ischemia / reperfusion-induced oxidative damage to mitochondria in rat liver.  Eur J Pharmacol. 2003;  465 163-170
• 16 Tomatsuri N, Yoshida N, Takagi T et al. Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats.  Int J Mol Med. 2004;  13 105-109
• 17 Ji L L, Fu R G, Waldrop T G et al. Myocardial response to regional ischemia and reperfusion in vivo in rat heart.  Can J Physiol Pharmacol. 1993;  71 811-817
• 18 Murin R, Drgova A, Kaplan P et al. Ischemia / reperfusion-induced oxidative stress causes structural changes of brain membrane proteins and lipids.  Gen Physiol Biophys. 2001;  20 431-438
• 19 Levin R M, Brendler K, Van Arsdalen K N et al. Functional response of the rabbit urinary bladder to anoxia and ischemia.  Neurourol Urodyn. 1983;  2 233-243
• 20 Lin A TL, Yang C H, Chen K K. Correlation of lipid peroxidation with energetic metabolism and contractile function in overdistention of the rabbit urinary bladder.  Neurourol Urodyn (Suppl). 1996;  15 426
• 21 Matsumoto S, Leggett R E, Levin R M. The effect of vitamin E on the ­response of rabbit bladder smooth muscle to hydrogen peroxide.  Mol Cell Biochem. 2003;  254 347-351
• 22 Halayko A J, Solway J. Molecular mechanisms of phenotypic plasticity in smooth muscle cells.  J Apply Physiol. 2001;  90 358-368
• 23 Absher M, Woodcock-Mitchell J, Mitchell J et al. Characterization of vascular smooth muscle cell phenotype in long-term culture. In Vitro Cell Dev.  Biol. 1989;  25 183-192
• 24 Hanai T, Matsumoto S, Ohnishi N et al. Serial changes of smooth muscle cell phenotypes in rat urinary bladder following partial outflow obstruction.  Adv Exp Med Biol. 2003;  539 293-296
• 25 Matsumoto S, Hanai T, Ohnishi N et al. Bladder smooth muscle cell phenotypic changes and implication of expression of contractile proteins (especially caldesmon) in rats after partial outlet obstruction.  Int J Urol. 2003;  10 339-345
• 26 Matsumoto S, Hanai T, Kurita T et al. Phenotypic changes in human bladder smooth muscle cell.  Acta Urologia Japonica. 2003;  49 715-719