A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection

Experimental models to study the effect of agents on penile erection usuall y include electrical stimulation of peripheral nerves in anesthetized anima ls combined with systemic or intracavernous injection of drugs. The objecti ve of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show po tential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intra venous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors v ardenafil x HCl (hereafter called vardenafil) and sildenafil were given int ravenously, and measurements were taken for 0-5 h. The effects of phentolam ine and milrinone were also evaluated. Vardenatil (0.1-3 mg/kg) induced dos e-dependent penile erections in conscious rabbits following i.v. administra tion. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administratio n of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect, Sildenafil was e ffective in this model after Lv. administration. The a-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous admini stration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treat ment of erectile dysfunction. This was demonstrated using compounds that ta rget different signaling pathways that induce smooth muscle relaxation in t he penis.