Figure 1.

((R)-2-({1-[(5-ethyl-1,3,4-thiadiazol-2-yl) carbamoyl]cyclopentyl}methyl) valeric acid) (UK-414,495), a selective inhibitor of neutral endopeptidase (NEP), dose-dependently enhanced pelvic nerve-stimulated (PNS) increases in vaginal blood flow (VBF) in the anaesthetized rabbit model of sexual arousal. Repetitive PNS, at submaximal stimulation frequencies, at 15 min intervals induced reproducible increases in VBF (solid circle). Infusion of increasing concentrations of UK-414,495 (at 1, 3, 10, 30 and 100 × IC₅₀ for rabbit native NEP) significantly enhanced the peak increase in VBF (open circles) compared with the mean baseline control flow increases. UK-414,495 had no effect on basal (unstimulated) VBF (open squares) compared with baseline control flow (solid square). Vehicle infusion had no effect on nerve-stimulated and unstimulated VBF (shaded circles and squares). All changes were monitored using laser Doppler technologies and data are expressed as mean ± SEM (n= 3–10), *P < 0.05, **P < 0.01 Student's t-test (paired vs. baseline control). Note that the small non-significant increases in basal VBF observed at 10 × IC₅₀ arose from one animal out of 10 where the baseline increased. At 45 min after the highest dose of UK-414,495, the nerve-mediated response was lost in a number of animals.