Role of the L‐arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins

In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10-6 M, NG-nitro-L-arginine (L-NNA) 10-7-10-4 M, and oxyhaemoglobin 10-5 M, but not by methylene blue (MB) 10-5 M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10-4 M and oxyhaemoglobin 10-5 M, but were unaffected by pyrogallol 10-4M, MB 10-6 M, and tetrodotoxin 10-6 M. MB 5 × 10-4-10-4 M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10-7-10-4 M and sodium nitroprusside 10-9-10-4 M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10-5 M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10-5 M. The response to sodium nitroprusside was unaffected by L-NNA 10-4 M, oxyhaemoglobin 10-5 M, and pyrogallol 10-4M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10-4 M and oxyhaemoglobin 10-5 M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10-5 M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged. The results confirm previous observations that relaxations of human corpus cavernosum induced by both NANC nerve stimulation and exogenous acetylcholine involve an agent derived from L-arginine. No NANC response to electrical stimulation was found in circumflex veins, where acetylcholine induced an endothelium-dependent relaxation, apparently independent of the L-arginine/nitric oxide pathway.