Inhibition of neuroeffector transmission in human vas deferens by sildenafil

Sildenafil (0.1-30 muM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor , induced inhibition of electrically evoked contractions of ring segments o f human vas deferens from 34 vasectomies. Zaprinast (0.1-100 muM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1- 100 muM) had no effect on neurogenic contractions. The inhibition in duced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a] quinoxaline-1-one (ODQ) (1-30 muM) but it was a bolished by the K+ channel blockers tetraethylammonium (TEA, 1 mM), iberiot oxin (0.1 muM) and charybdotoxin (0.1 muM). Sildenafil, zaprinast and SNP d id not affect the contractions induced by noradrenaline. SNP (10 muM) cause d elevation of cyclic GMP levels that was potentiated by sildenafil (10 muM ) and zaprinast (100 muM). ODQ (10 muM) inhibited the increase in cyclic GM P. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca2+-activated K+ cha nnels.