THE EFFECT OF THE SPECIFIC PHOSPHODIESTERASE (PDE) INHIBITORS ON HUMAN AND RABBIT CAVERNOUS TISSUE IN-VITRO AND IN-VIVO

Purpose: Phosphodiesterases (PDE) are key enzymes in the regulation of the smooth muscle tone. Experimental studies showed PDE III and V-iso enzymes to play an important role in the smooth muscle tone regulation of corpus cavernosum. Recently, a specific PDE III-inhibitor (milrino ne) and a PDE V-inhibitor (sildenafil) were introduced in clinical stu dies. An experimental study was done to examine a potential role of PD E-inhibitors in the treatment of erectile dysfunction. Materials and M ethods: In the organ bath, strips from human and rabbit corpus caverno sum were precontracted and increasing doses of PDE inhibitors were add ed. In patients with erectile dysfunction as well as in rabbits, intra cavernous injections of milrinone were done. Results: PDE-inhibitors d ose-dependently relaxed human and rabbit corpus cavernosum strips. In the precontracted human cavernous tissue, milrinone and sildenafil wer e equally potent and efficacious in vitro. In the rabbit, milrinone in duced slight tumescence but dramatic circulatory side effects. In pati ents, penile tumescences as well as full erections were observed. Conc lusions: Milrinone strongly relaxes human cavernous smooth muscle cell s but it exhibits low relaxant effects in the rabbit cavernous tissue. In human tissue, sildenafil was equieffective with milrinone in vitro . In vivo, milrinone induced a good erectile response in humans but a poor erectile effect in rabbits. Our results support a possible potent ial for selective PDE-III and -V inhibitors in the treatment of impote nce and give further evidence that the rabbit is an animal model of li mited value to study the effects of drugs on cavernous smooth muscle t one regulation in vivo.