IN VITRO PHARMACOLOGICAL STUDY OF SOME DRUGS USED IN PENILE ERECTION DYSFUNCTION

Abstract

The present study was designed to investigate the possible mechanisms contributing to the action of sildenafil, the newly introduced drug proven to promote erectile functions. Sildenafil was shown to facilitate relaxation of the smooth muscle of corpus cavernosum in vitro, the essential process leading to penile erection. RCC, rat anococcygeus muscle and rat aortic rings were used to examine the effect of sildenafil on. nitrergic transmission. An in vitro comparison of sildenafil and other drugs used for the same purpose on erectile functions was also conducted on RCC. The main findings can be summarized as follows: l. Corporal smooth muscle relaxation elicited by EFS is due to NANC neuronal­ dependent formation of NO. The experimental evidence for this hypothesis is that chemical agents known to inhibit the formation or target cell actions of NO markedly inhibited EFS-induced relaxation. This study demonstrated also the important role of arginine/nitric oxide pathway in mediating relaxation of penile smooth muscle necessary for erection. 2. Sildenafil may act through the amplification of neuronal NO/cGMP pathway, consequent to the inhibition ofPDE type 5. Sildenafil showed clear potentiation of the amplitude and duration ofNANC relaxation of both RCC and rat anococcygeus muscle. Similar conclusion was obtained when studied on rat aortic rings, where sildenafil was shown to augment NO-induced relaxation. Its action was shown to involve a combination of pre- and post-synaptic mechanisms. 3. Sildenafil may act by more than one mechanism, since it evoked smooth muscle relaxation of RCC. This relaxant effect was independent ofNO/cGMP pathway as L­ NNA and MB failed to affect this action significantly both in RCC and rat aortic rings. . This action was also endothelium independent.