A previous study showed that
DA-8159, a potent
type 5 phosphodiesterase inhibitor, enhanced the relaxation of the smooth muscles in the normal rabbit corpus cavernosum. In this study, we investigated the in vitro effects of
DA-8159 on cavernosal smooth muscle relaxation and the in vivo erectogenic potential in diabetic rabbits, since
erectile dysfunction is a well-known sequela of
diabetes mellitus.
Diabetes mellitus was induced in male New Zealand White rabbits with
alloxan monohydrate. Cavernosal strips from age-matched control and 8-week diabetic animals were mounted in organ
baths. The relaxation responses to
sodium nitroprusside (10(-9)--10(-5) M), a
nitric oxide donor, were assessed in the presence or absence of
DA-8159 (10(-9)--10(-6) M). For the penile erection test,
DA-8159 was given orally (1-10 mg/kg) to diabetic rabbits and the length of the uncovered penile shaft was measured in a time-course manner in the presence or absence of intravenous
sodium nitroprusside. The
sodium nitroprusside-stimulated relaxations were significantly impaired in the corpus cavernosum from the diabetic group (IC(50)=1.07 x 10(-6) M following 8 weeks of
diabetes mellitus; compared with 0.48 x 10(-6) M for age-matched controls).
DA-8159 significantly and dose-dependently enhanced the
sodium nitroprusside-stimulated relaxation in the diabetic groups. In addition,
DA-8159 induced a dose-dependent penile erection in diabetic rabbits, which was potentiated by intravenous
sodium nitroprusside. These results suggest that
DA-8159 is an effective treatment for diabetic
erectile dysfunction but further evaluation of the efficacy on human needs to be performed.