Nonadrenergic, noncholinergic relaxation of human isolated corpus cavernosum induced by scorpion venom

Abstract

Objectives. To examine the effects of Tityus serrulatus scorpion venom (TSV) on human corpus cavernosum (HCC) using a bioassay cascade. Priapism is occasionally observed in scorpion envenomation, mostly in children. Methods. HCC strips were suspended in a cascade system and superfused with aerated and warmed Krebs’ solution at 5 mL/min. Noradrenaline (3 μmol/L) was infused to induce a submaximal contraction of the HCC strips. The release of cyclooxygenase products was prevented by infusing indomethacin (6 μmol/L). Results. N ω-nitro- l-arginine methyl ester (10 μmol/L; n = 10) increased the tone of the preparations and significantly reduced ( P <0.01) the acetylcholine (ACh) and TSV-induced relaxations. Subsequent infusion of l-arginine (300 μmol/L) partially reversed the increased tone and significantly restored the relaxations induced by TSV and ACh ( P <0.01). The soluble guanylyl cyclase inhibitor ODQ (10 μmol/L; n = 8) markedly reduced ( P <0.01) the relaxations induced by TSV, ACh, glyceryl trinitrate, and bradykinin. 7-Nitroindazole (10 μmol/L; n = 8) inhibited the relaxations induced by TSV by 84% ( P <0.01) and also caused small, but significant, reductions in the ACh and bradykinin-induced HCC relaxations ( P <0.05). Atropine (1 μmol/L; n = 6) abolished the relaxations evoked by ACh ( P <0.01), but had no effect on those elicited by TSV. Tetrodotoxin (1 μmol/L; n = 6) abolished the relaxations induced by TSV ( P <0.01) and also reversed the established TSV-induced relaxation (n = 4). Conclusions. Our results indicate that TSV relaxes HCC through the release of nitric oxide from nonadrenergic, noncholinergic (NANC) nerves. The elucidation of the mechanism responsible for the TSV-induced relaxations might be useful for a better understanding of the development of priapism in cases of scorpion envenomation.