Pro-erectile effect of vardenafil: In vitro experiments in rabbits and in vivo comparison with sildenafil in rats

Objectives: To assess pro-erectile responses to vardenafil, a new selective PDE5 inhibitor, in vitro in isolated rabbit corpora cavernosa, and in vivo in anaesthetized rats. Methods: Rabbit cavernosal strips were precontracted with 10 muM phenylephrine. Dose-response relaxation curves to cumulative dosings of vardenafil (1 nM-10 muM) were constructed alone and in the presence of 10 mM L-NAME. Relaxation responses to electrical field stimulation (EFS) (2 Hz, 2 ms, 10 V) were compared in control preparations and in the presence of vardenatil (1-10 nM). Male Sprague-Dawley rats were anaesthetized with urethane and prepared for measurement of blood pressure and intracavernous pressure. Erectile responses (ICPmax/dBP x 100) to cavernous nerve submaximal stimulation (10 Hz, 1 ms, 0.45-1.6 V) were determined before, and 3, 10 and 23 min after i.v. administration of saline, vardenafil or sildenafil (0.1, 1 mg/kg). Results: Vardenafil was effective in relaxing precontracted rabbit cavernosal strips (IC50 54+/-18 nM). This relaxing activity was partially antagonized with 10 mM L-NAME, increasing the IC50 to 620+/-81 nM. Vardenafil significantly increased (more than 4 times) relaxation of precontracted rabbit cavernosal strips to EFS at 10 nM. In anaesthetized rats, erectile responses were significantly facilitated 3 and 13 min after 0.1 and 1 mg/kg vardenafil was administered. In contrast, 1 mg/kg sildenafil only significantly increased erectile responses at 3 min post-injection. Conclusions: Vardenafil relaxes rabbit corpus cavernosum in vitro and is effective at a lower dose than sildenafil in facilitating erectile responses to cavernous nerve stimulation in anaesthetized rats. (C) 2003 Elsevier B.V. All rights reserved.