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 microM phenylephrine. Dose-response relaxation curves to cumulative dosings of vardenafil (1 nM-10 microM) 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 vardenafil (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.
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 microM phenylephrine. Dose-response relaxation curves to cumulative dosings of vardenafil (1 nM-10 microM) 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 vardenafil (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.
Authors: Haroldo A Toque; Fernanda B M Priviero; Saiprasad M Zemse; Edson Antunes; Cleber E Teixeira; R Clinton Webb Journal: Clin Exp Pharmacol Physiol Date: 2008-10-15 Impact factor: 2.557
Authors: A Kun; V V Matchkov; E Stankevicius; A Nardi; A D Hughes; H J Kirkeby; J Demnitz; U Simonsen Journal: Br J Pharmacol Date: 2009-10-20 Impact factor: 8.739