Short-term histopathologic effects of different intracavernosal agents on corpus cavernosum and antifibrotic activity of intracavernosal verapamil: an experimental study

Urology. 2001 Sep;58(3):487-92. doi: 10.1016/s0090-4295(01)01211-0.


Objectives: To evaluate the short-term effects of different intracavernosal agents and to investigate the antifibrotic effect of verapamil combined with these intracavernosal agents.

Methods: Forty-five Sprague-Dawley rats weighing 400 to 500 g each (mean weight 435.27 +/- 13.65 g) were equally divided into nine groups (n = 5). Papaverine (group 1), alprostadil (group 2), sodium nitroprusside (group 3), and verapamil (group 4) were injected alone intracavernously in 0.2-mL doses. Verapamil combined with papaverine, alprostadil, and sodium nitroprusside in 0.2-mL doses (0.1 mL verapamil and 0.1 mL vasoactive agent) were injected in groups 5 through 7. Group 8 was kept as a control group without injection, and isotonic saline alone was injected in group 9 during the same period. The intracavernous injection was done twice weekly with a 4-day interval. At the end of the study, total penectomy and multiple liver biopsies were performed to evaluate the histopathologic effects of the vasoactive agents and to test the liver function.

Results: In all groups, the structure of the corpora cavernosa was well preserved generally and appeared similar to the control tissue. However, localized edema, fibrosis, macrophage infiltration, and polymorphonuclear leukocytes were found only at the injection site. Although these findings were not different from the findings in the saline and alprostadil groups, they were slightly more extensive in the papaverine and sodium nitroprusside alone groups and also in the vasoactive agent plus verapamil groups. Although mononuclear lymphocyte infiltration was found in the portal areas, advancing into the liver parenchyma, the liver function tests were within normal limits.

Conclusions: We observed that intracavernous injection, except with nitroprusside, caused focal intracavernosal fibrosis and edema. We believe these effects might not be caused by just the drug, but also by needle trauma, since general fibrosis was not observed in the short term. However, nitroprusside has a severe fibrotic effect on cavernosal tissue in the short term. Moreover, intracavernous verapamil injection could not prevent the fibrosis in the short term.

MeSH terms

  • Alprostadil / pharmacology
  • Alprostadil / toxicity
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / toxicity
  • Chemical and Drug Induced Liver Injury
  • Disease Models, Animal
  • Erectile Dysfunction / drug therapy
  • Fibrosis
  • Humans
  • Injections
  • Liver / drug effects
  • Liver Diseases / diagnosis
  • Liver Function Tests
  • Male
  • Nitroprusside / pharmacology
  • Nitroprusside / toxicity
  • Papaverine / pharmacology
  • Papaverine / toxicity
  • Penile Diseases / chemically induced*
  • Penile Diseases / pathology
  • Penile Diseases / prevention & control*
  • Penile Erection / drug effects*
  • Penis / anatomy & histology
  • Penis / drug effects*
  • Penis / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilator Agents / pharmacology*
  • Vasodilator Agents / toxicity*
  • Verapamil / pharmacology*
  • Verapamil / toxicity


  • Calcium Channel Blockers
  • Vasodilator Agents
  • Nitroprusside
  • Verapamil
  • Papaverine
  • Alprostadil