Effects of phosphodiesterase V inhibition on nitric oxide-mediated relaxation responses in guinea pig trachea.

In the present study, we aimed to evaluate the effects of PDE V inhibition on NO-mediated relaxation responses in isolated guinea pig trachea. Under the NANC conditions, tracheal preparations were contracted with histamine (100 microm/l). When contraction had reached a plateau, relaxation responses to electrical field stimulation (EFS, 60 V, 0.5 ms, 5-10 Hz) were determined before and after incubation of the tracheal ring with L-NAME (1 mmol/l), a NO synthase inhibitor. L-NAME significantly inhibited the relaxation responses and this inhibitory effect was reversed by L-arginine (1 mmol/l), a precursor of NO, but was not affected by D-arginine. In addition, cumulative application of the NO donors, 3-morpholino-sydnonimine (SIN-1) and sodium nitroprusside (SNP), caused concentration-dependent relaxation of tissues precontracted with histamine. The selective PDE type V inhibitor zaprinast at EC50 concentration (30 micromol/l) significantly potentiated EFS-induced NANC relaxations and relaxant responses to SIN-1 and SNP. In conclusion, these data support the hypothesis that NO is a mediator of NANC relaxations of guinea pig tracheal rings and PDE V inhibition potentiates NO-mediated relaxation.
(Copyright 2004 S. Karger AG, Basel)