The effect of DA-8159 on corpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits.
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.
Kang
Kyung Koo
KK
Research Institutes, Dong-A Pharmaceutical Company, 47-5 Sanggal, Kiheung, Youngin, 449-900 Kyunggi, Korea. kangkk@empal.com
Choi
Seul Min
SM
Ahn
Gook Jun
GJ
Kwon
Jong Won
JW
Kim
Won Bae
WB
D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001786:Blood Glucose; D009599:Nitroprusside; D010656:Phenylephrine; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C419664:udenafil; D000096926:Benzenesulfonamides