Hydroxyfasudil ameliorates penile dysfunction in the male spontaneously hypertensive rat.
Τίτλος | Hydroxyfasudil ameliorates penile dysfunction in the male spontaneously hypertensive rat. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Saito, M., Ohmasa F., Dimitriadis F., Tsounapi P., Sejima T., Shimizu S., Kinoshita Y., & Satoh K. |
Journal | Pharmacol Res |
Volume | 66 |
Issue | 4 |
Pagination | 325-31 |
Date Published | 2012 Oct |
ISSN | 1096-1186 |
Λέξεις κλειδιά | 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Animals, Cyclic GMP, Erectile Dysfunction, Gene Expression Regulation, Hypertension, Male, Nitric Oxide Synthase Type III, Penis, Phosphorylation, Rats, Rats, Inbred SHR, Rats, Wistar, rho-Associated Kinases, RNA, Messenger |
Abstract | Hypertension represents a major risk factor for erectile dysfunction. Although the etiology of hypertension-induced erectile dysfunction is multifactorial and still unknown, Rho-Rho kinase pathway is one of the key factors. To investigate whether administration of hydroxyfasudil, a Rho kinase inhibitor could prevent dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the SHR (spontaneously hypertensive rat), twelve-week-old male SHRs were treated with hydroxyfasudil (3 or 10 mg/kg, i.p.) once a day for 6 weeks. Wistar rats and SHRs treatment with vehicle were used as age-matched controls. Penile cGMP concentrations and Rho kinase activities were determined, and penile function was estimated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The participation mRNA levels of eNOS and participation protein levels of eNOS and phosphorylated eNOS were investigated by quantitative real-time PCR methods and immunoblot analysis, respectively. The SHR showed significantly decreased cGMP concentrations, increased Rho kinase activities, norepinephrine-induced hyper-contractions, and acetylcholine-induced hypo-relaxations in the penile tissue. Treatment with hydroxyfasudil significantly improved the decreased penile cGMP concentrations, the increased Rho kinase activities, the increased norepinephrine-induced contractions, and the decreased acetylcholine-induced relaxation in a dose-dependent manner. Although there were no significant differences in expression protein levels of eNOS among any of the groups, down-regulation of eNOS mRNAs as well as phosphorylated eNOS were significantly ameliorated after treatment with hydroxyfasudil. Our data suggest that hydroxyfasudil ameliorates hypertension-associated dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle possibly via inhibition of the Rho-Rho kinase pathway and activation of NO-eNOS pathway in the SHR. |
DOI | 10.1016/j.phrs.2012.06.005 |
Alternate Journal | Pharmacol Res |
PubMed ID | 22750666 |