Synergistic effects of sildenafil on relaxation of rabbit and rat cavernosal smooth muscles when combined with various vasoactive agents.
OBJECTIVE
To evaluate which vasoactive agents have synergistic effects on the cavernosal smooth muscles of rabbits and rats when the agents are combined with sildenafil.


METHODS
Relaxation responses of cavernosal smooth muscle to single agents (phentolamine, moxisylyte, sodium nitroprusside, forskolin, vasoactive intestinal peptide, VIP, papaverine and sildenafil) in the rabbit, and prostaglandin-E1 and sildenafil in the rat, and to combinations of each agent plus sildenafil, were assessed in vitro. The response to sildenafil of the rabbit strips with and without incubation with l-arginine (1 mmol/L) for 20 min was also evaluated. The effective concentrations for a half-maximal response of single agents and combination solutions were compared.


RESULTS
All single agents induced concentration-dependent relaxation of the rabbit and rat cavernosal smooth muscles. There was significant synergism on rabbit cavernosal smooth muscle when the sildenafil was combined with forskolin, sodium nitroprusside, VIP or phentolamine. There was also significant synergism with sildenafil plus prostaglandin-E1 in rat cavernosal muscles. There were no synergistic effects of combinations of sildenafil plus moxisylyte, papaverine or l-arginine.


CONCLUSIONS
These results suggest potentially effective combined therapies of sildenafil and intraurethral or intracavernosal prostaglandin-E1, intracavernosal forskolin or VIP, or oral phentolamine for patients with erectile dysfunction who have no success after monotherapy with these agents.
Seo
K K
KK
Department of Urology and Physiology, College of Medicine, Chung-Ang University, Seoul, Korea.
Kim
S C
SC
Jun
I O
IO
Oh
M M
MM
Lee
M Y
MY
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000627:therapeutic use; D005576:Colforsin / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010646:Phentolamine / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D011687:Purines; D011817:Rabbits; D051381:Rats; D000068677:Sildenafil Citrate; D013450:Sulfones
D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011459:Prostaglandins E, Synthetic; D011687:Purines; D013450:Sulfones; D005576:Colforsin; D000068677:Sildenafil Citrate; D010646:Phentolamine