Edaravone Ameliorates Diabetes-Induced Dysfunction of NO-Induced Relaxation in Corpus Cavernosum Smooth Muscle in the Rat

Authors


Motoaki Saito, MD, PhD, Department of Pathophysiological and Therapeutic Science, Division of Molecular Pharmacology, Tottori University School of Medicine, 86 Nishimachi, Yonago 683-8503, Japan. Tel: +81-859-38-6162; Fax: +81-859-38-6160; E-mail: saitomo@med.tottori-u.ac.jp

ABSTRACT

Introduction.  Diabetes mellitus (DM) represents a major risk factor for erectile dysfunction (ED). Although the etiology of diabetes-induced ED is multifactorial and still unknown, reactive oxygen species are thought to be one of the key factors.

Aim.  The aim of this article is to investigate whether administration of edaravone, a free radical scavenger, could prevent type 1 diabetes-induced dysfunction of nitric oxide (NO)-induced relaxation in corpus cavernosum smooth muscle in the rat.

Methods.  Six-week-old male Wistar rats were randomly divided into three groups. One group was treated with citrate-phosphate buffer plus normal saline (group Cont), whereas in the other two groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally [i.p.]). Subsequently, the diabetic rats were treated for 4 weeks either with edaravone (10 mg/kg/day, i.p.; group DM + E) or with normal saline (group DM).

Main Outcome Measures.  Serum glucose and malondialdehyde levels as well as penile cyclic guanosine monophosphate (cGMP) concentrations were determined, and penile function was estimated by organ bath studies with norepinephrine-mediated contractions and acetylcholine-mediated relaxations. The participation mRNA levels of muscarinic M3 receptors, neuronal nitrous oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), and participation protein levels of nNOS, eNOS, phosphorylated nNOS, and phosphorylated eNOS were investigated by quantitative real-time polymerase chain reaction (PCR) and immunoblot analysis, respectively.

Results.  Treatment with edaravone prevented partially but significantly the decreased body and penile weight induced by diabetes. Treatment with edaravone significantly improved the increased diabetes-induced malondialdehyde levels, the decreased penile cGMP concentrations, the increased diabetes-induced norepinephrine-mediated contractions, and the decreased acetylcholine-mediated relaxation. Although there were no significant differences in expression levels of mRNAs in nNOS, diabetes-induced upregulation of muscarinic M3 receptor and iNOS mRNAs as well as diabetes-induced downregulations of eNOS, phosphorylated nNOS, and phosphorylated eNOS were significantly prevented by edaravone.

Conclusions.  Edaravone decreases the oxidative insult in the penile corpus cavernosum by ameliorating the NO–NOS system and thus preventing partially the developing ED in DM in the rat. Ohmasa F, Saito M, Tsounapi P, Dimitriadis F, Inoue S, Shomori K, Shimizu S, Kinoshita Y, and Satoh K. Edaravone ameliorates diabetes-induced dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the rat. J Sex Med 2011;8:1638–1649.

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