MP43-15 BAY41-2272 ENHANCED SILDENAFIL INHIBITED MIGRATION IN RAT PENILE SMOOTH MUSCLE CELLS.

INTRODUCTION AND OBJECTIVES: In this study, we focused on whether olmesartan, an angiotensin II receptor blocker, or nifedipine, an L-type calcium channel blocker, could prevent dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the spontaneously hypertensive rat (SHR). METHODS: Twelve-week-old male SHRs, and Wistar rats as aged-matched normotensive controls were used in this study. The treatment groups were administered olmesartan (1 or 3mg/kg, per orally (p.o.); Olm1 or Olm3, respectively) or nifedipine (30mg/kg, p.o.; Nif) for six weeks daily. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholineinduced relaxations. Penile cGMP concentrations and mRNA levels of eNOS and nNOS were investigated. RESULTS: The SHR showed significantly increased blood pressure (BP), norepinephrine-induced hyper-contractions, acetylcholine-induced hypo-relaxations, decreased cGMP concentrations, and decreased eNOS and nNOS mRNA levels in the penile tissue. Treatment with high dose of olmesartan significantly decreased BP, significantly increased the penile cGMP concentrations, partially normalized the eNOS and nNOS mRNA levels, significantly decreased the norepinephrine-induced contractions, and normalized the acetylcholineinduced relaxation compared to the SHR. Nifedipine significantly decreased BP, increased cGMP, and normalized the hyper-contractions and hypo-relaxations observed in the SHR group, while the mRNA levels of eNOS and nNOS were significantly lower compared to the Wistar. CONCLUSIONS: Our results indicate that the dysfunction in the SHR penile tissue could be better reversed by olmesartan treatment and to a slightly lesser extent by nifedipine treatment.