Pro-erectile effect of vardenafil: in vitro experiments in rabbits and in vivo comparison with sildenafil in rats.
OBJECTIVE
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.
Giuliano
F
F
Pelvipharm Laboratories, CNRS Bat 5, 1 avenue de la Terrasse, 91140 Gif-sur-Yvette, France. giuliano@cyber-sante.org
Bernabe
J
J
Alexandre
L
L
Niewoehner
U
U
Haning
H
H
Bischoff
E
E
D000818:Animals; D046508:Culture Techniques; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011336:Probability; D011687:Purines; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D000068677:Sildenafil Citrate; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068677:Sildenafil Citrate