In vitro viability of human cavernosal endothelial and fibroblastic cells after exposure to papaverine/phentolamine and prostaglandin E1.
OBJECTIVE
To investigate the influence of commercially available vasoactive drugs on human cavernosal endothelial and fibroblastic cells in vitro, as although corporal fibrosis is a well known side-effect of intracavernosal injection therapy for erectile dysfunction, the possible detrimental effect of these agents on the endothelium lining the cavernosal vascular spaces is uncertain.


METHODS
Cultured primary endothelial (13) and fibroblastic cells (12), obtained from potent patients undergoing penile surgery, were exposed to different physiological dilutions of prostaglandin E1 (PGE1), papaverine/phentolamine or the respective triple-mix of these agents for 30 min. Viable cells were counted and cell metabolic activity measured in these cultures 48 h after drug exposure.


RESULTS
There was a significant dose-dependent decrease in the viable cell count after exposure to papaverine-containing formulations, probably because of the low pH of this substance. This cytotoxic effect was more pronounced in endothelial than in fibroblastic cells, and was not apparent in the PGE1 groups. The relative increase in cell metabolic activity in cultures affected by a moderate cytotoxic effect indicated a regenerative process.


CONCLUSIONS
These comparative results in endothelial and fibroblastic cell cultures suggest that the endothelium rather than the interstitium of the corpus cavernosum is more sensitive to side-effects produced by intracavernosal injection therapy with papaverine. Thus, unfavourable consequences on the function of the endothelial layer might be as important as the risk of interstitial fibrosis. As these effects were not detected for PGE1 this drug should be preferred to papaverine in clinical practice.
Pilatz
Adrian
A
Department of Urology and Paediatric Urology, Hannover Medical School, Hannover, Germany.
Schultheiss
Dirk
D
Gabouev
Alexander I
AI
Schlote
Norbert
N
Mertsching
Heike
H
Jonas
Udo
U
Stief
Christian G
CG
D000527:Alprostadil / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010413:Penis / Q000473:pathology*; D010646:Phentolamine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D010208:Papaverine; D000527:Alprostadil; D010646:Phentolamine