Experimental evidence for endothelium dependent relaxation and neuronal nitric oxide in corpus cavernosum

It is known that penile erection is mediated primarily through the release of a nonadrenergic noncholinergic (NANC) neurotransmitter which has been recently identified as nitric oxide (NO). To evaluate whether the endothelium is involved in neurally mediated relaxation in corpus cavernosum, we determined electrical field stimulation (EFS) induced relaxation in both the presence and absence of endothelium, and we tested the effect of an inhibitor of NO synthase. N(G)-nitro-L-arginine (NOARG), in the absence of endothelium to examine if de-endothelialized tissue can still generate NO. Isolated corpus cavernosal strips from New Zealand White rabbits were used for isometric tension study using organ chambers. The endothelium was removed through denuding tissue. After the tissue was contracted with norepinephrine, EFS was performed at frequencies of 5, 15 and 40 hZ in the presence of guanethidine and atropine to evaluate NANC-selective neural relaxation. The relaxation induced by EFS was observed after preincubation with NOARG(10^-4 M) for 30 minutes. L-arginine (10^-3 M) was then added for 30 minutes in the presense of NOARG before a second set of EFS studies were performed. Following norepinephrine precontration. EFS relaxed corporal strips in both the intact and de-endothelialized strips. However, de-endothelialization significantly impaired EFS induced relaxation (p < 0.05). NOARG attenuated relaxation induced by EFS and the addition of L-arginine reversed the inhibitory effect of NOARG in the strips with endothelium. In the strips without endothelium. NOARG still inhibited EFS induced relaxation. This relaxation was reversed by the addition of L-arginine. From these results, NO may be released by the neurons of corpus cavernosum and NANC neurally mediated relaxation of corpus cavernosum has an endothelium dependent component. Therefore, the impairment in the function of endothelium in the penile sinusoidal spaces could cause an insufficient cavernosal relaxation and produce an erectile dysfunction.