title: Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model.
abstract: Possible effect of olmesartan, an angiotensin II receptor blocker (ARB), or nifedipine, an L-type calcium channel blocker, on penile dysfunction in the spontaneously hypertensive rat (SHR) was investigated in this study. Twelve-week-old male SHRs were treated with olmesartan (1 or 3 mg/kg, per orally (p.o.)) or nifedipine (30 mg/kg, p.o.) once a day for 6 weeks. Wistar rats and SHRs with vehicle treatment were used as controls. Penile cGMP and malondialdehyde concentrations, and mRNA levels of endothelial and neuronal NO synthase (eNOS and nNOS) were measured. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The SHR showed significantly increased blood pressure, decreased cGMP concentrations, increased malondialdehyde concentrations, decreased eNOS and nNOS mRNA levels, norepinephrine-induced hyper-contractions, and acetylcholine-induced hypo-relaxations in the penile tissue compared to the Wistar rat. Both nifedipine and olmesartan significantly decreased blood pressure, increased cGMP and normalized the hyper-contractions and hypo-relaxations observed in the SHR group. However, not nifedipine but olmesartan improved the malondialdehyde concentrations and increased mRNA levels of eNOS and nNOS in the penis. Our results indicate that the hypertension-associated penile dysfunction might be treated with ARBs such as olmesartan better than calcium channel blockers, such as nifedipine.
authors.affiliation: Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Shimizu
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsounapi
authors.forename: Masashi
authors.initials: M
authors.lastname: Honda
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects*; D000818:Animals; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D057911:Angiotensin Receptor Antagonists; D002121:Calcium Channel Blockers; D008315:Malondialdehyde; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP