PURPOSE: Phosphodiesterases (PDE) are key enzymes in the regulation of the smooth muscle tone. Experimental studies showed PDE III and V-isoenzymes to play an important role in the smooth muscle tone regulation of corpus cavernosum. Recently, a specific PDE III-inhibitor (milrinone) and a PDE V-inhibitor (sildenafil) were introduced in clinical studies. An experimental study was done to examine a potential role of PDE-inhibitors in the treatment of erectile dysfunction. MATERIALS AND METHODS: In the organ bath, strips from human and rabbit corpus cavernosum were precontracted and increasing doses of PDE inhibitors were added. In patients with erectile dysfunction as well as in rabbits, intracavernous injections of milrinone were done. RESULTS: PDE-inhibitors dose-dependently relaxed human and rabbit corpus cavernosum strips. In the precontracted human cavernous tissue, milrinone and sildenafil were equally potent and efficacious in vitro. In the rabbit, milrinone induced slight tumescence but dramatic circulatory side effects. In patients, penile tumescences as well as full erections were observed. CONCLUSIONS: Milrinone strongly relaxes human cavernous smooth muscle cells 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 potential for selective PDE-III and -V inhibitors in the treatment of impotence and give further evidence that the rabbit is an animal model of limited value to study the effects of drugs on cavernous smooth muscle tone regulation in vivo.
PURPOSE: Phosphodiesterases (PDE) are key enzymes in the regulation of the smooth muscle tone. Experimental studies showed PDE III and V-isoenzymes to play an important role in the smooth muscle tone regulation of corpus cavernosum. Recently, a specific PDE III-inhibitor (milrinone) and a PDE V-inhibitor (sildenafil) were introduced in clinical studies. An experimental study was done to examine a potential role of PDE-inhibitors in the treatment of erectile dysfunction. MATERIALS AND METHODS: In the organ bath, strips from human and rabbit corpus cavernosum were precontracted and increasing doses of PDE inhibitors were added. In patients with erectile dysfunction as well as in rabbits, intracavernous injections of milrinone were done. RESULTS: PDE-inhibitors dose-dependently relaxed human and rabbit corpus cavernosum strips. In the precontracted human cavernous tissue, milrinone and sildenafil were equally potent and efficacious in vitro. In the rabbit, milrinone induced slight tumescence but dramatic circulatory side effects. In patients, penile tumescences as well as full erections were observed. CONCLUSIONS:Milrinone strongly relaxes human cavernous smooth muscle cells 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 potential for selective PDE-III and -V inhibitors in the treatment of impotence and give further evidence that the rabbit is an animal model of limited value to study the effects of drugs on cavernous smooth muscle tone regulation in vivo.
Authors: Matthias E Werner; Andrea L Meredith; Richard W Aldrich; Mark T Nelson Journal: Am J Physiol Regul Integr Comp Physiol Date: 2008-05-14 Impact factor: 3.619
Authors: Stefan Uckert; Petter Hedlund; Eginhard Waldkirch; Michael Sohn; Udo Jonas; Karl-Erik Andersson; Christian G Stief Journal: World J Urol Date: 2004-03-26 Impact factor: 4.226