Erectile Function Is Improved in Aged Rats by PnTx2‐6, a Toxin from Phoneutria nigriventer Spider Venom

Abstract

Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED. PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats. ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M). The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression. PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.