Avaliação in vitro e in vivo dos efeitos do ativador da guanilil ciclase soluvel BAY 41-2272 na ereção peniana / In vitro and in vivo effects of the soluble guanilyl cyclase BAY 41-2272 on penile erection

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Penile erection is a physiologic event that includes psychic, neural and vascular mechanisms and involves the interaction of smooth muscle neural stimulation and releasing of relaxant and contractile agents from endothelium. The nitric oxide (NO) - soluble guanilyl cyclase (sGC) - cGMP system is the most significant and efficient mechanism of penile erection. BAY 41-2272 was recently identified as a potent sGC stimulator in a NO-independent manner. Therefore, the present study aimed to evaluate the influence of sGC-cGMP and adenylyl cyclasecAMP pathways and potassium channel in corpus cavernosum relaxing response ind uced by BAY 41-2272; to evaluate the performance of BAY 41-2272 to induce penile erection in vivo. For in vitro studies, rabbit, rat and human corpus cavernosum strips were mounted in a 10-ml organ bath containing Krebs solution (37OC, 95%02 / 5%C02). Each strip was connected to isometric transducer which was connected to a data acquisition system. Therefore, cGMP content was determined by ElA kit in rat corpus cavernosum in the absence or presence of BAY 41-2272 (1 jlM) ar SNP (1jlM). For in vivo studies, the Wistar rat right carotid was cannulated to mean arterial pressure measurement and left corpus cavernosum was cannulated to registrate the intracavernous pressure throught pressure transducers connected to a data acquisition system. The right corpus cavernosum was cannulated to drug administration. The cavernous nerve was exposed to receive electrical field stimulation in different frequencies. Thus, the addition of BAY 41-2272 (0.01 - 10 jlM) relaxed, in a concentration dependent manner, the corpus cavenosum smooth muscle strips of rabbit, rat and humano The relaxing effects were reduced in the presence of OOQ (10 jlM) or L-NAME (100 !-1M). However, rolipram and potassium channel blockers apamin, charibdotoxin, 4-aminopiridin, tetraethylamonium and glibenclamide not affect significantly the relaxation of rabbit and human corpus cavernosum strips. In rabbit, BAY 41-2272 increased the relaxation induced by electrical and exogenous nitric oxide stimulation. Moreover, BAY 41-2272 increased significantly the cGMPc levei in rat corpus cavernosum strip. On the other hand, in the in vivo studies BAY 41-2272 administration was able to increase the intracavernous pressure induced by electrical stimulation without affect mean arterial pressure. In conclusion, our results showed that BAY 41-2272 was able to induce smooth muscle relaxation of corpus cavernosum in vitro, in different species by a mechanism which involves mainly the soluble guanylyl cyclase stimulation and increase in cGMP level. Moreover, BAY 41-2272 improved the penile erection induced by cavernous nerve stimulation in anesthetized rats

ASSUNTO(S)

corpo cavernoso nitric oxide erectile dysfunction disfunção eretil oxido nitrico corpus cavernosum

ACESSO AO ARTIGO

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