Improvement of relaxation in Type II diabetic mice corpus cavernosum by PhTx2‐6 toxin from Phoneutria nigriventer spider

Type II diabetes mellitus (T2DM) is a major risk factor for development of erectile dysfunction (ED). Mechanisms causing ED in T2DM are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. The toxin PhTx2‐6 purified from this venom inhibits sodium (Na+) channel inactivation in neuronal‐type Na+ channels. We hypothesize that PhTx2‐6 potentiates cavernosal relaxation in T2DM mice. Cavernosal strips were pre‐contracted with phenylephrine (10−5 M) and relaxed by electrical field stimulation (EFS) in the presence or absence of PnTx2‐6 (10−8 M). cGMP levels from mice tissue were determined after stimulation with PhTx2‐6 in presence or absence of L‐NAME (10−4M). Results showed that PhTx2‐6 enhanced cavernosal relaxation in diabetic mice (± 65%) and the toxin was not able to reverse the inhibition by L‐NAME. cGMP levels are increased by PhTx2‐6 (± 1.57 vs. basal ±0.86), however L‐NAME abolished this enhancement. We conclude that PhTx2‐6 facilitates penile relaxation in diabetic mice probably via increasing NO release and consequently cGMP production. This toxin may be an important tool for development of new therapeutic approaches to treat ED in T2DM.