Figure 1.

nNOS^–/– mice have delayed gastric emptying and loss of NO-dependent NANC relaxation. Gastric emptying in (a) wild-type (WT) mice and (b) nNOS^–/– mice. As described in Methods, phenol red–labeled saline (circles), 10% dextrose (triangles), or 20% dextrose (squares) was instilled into the stomachs of groups of mice, five to ten animals for each time point. The mice were sacrificed at the indicated times to determine the fraction of phenol red remaining in the stomachs as a measure of gastric emptying. Individual data points represent the mean (± SEM) for five to 10 determinations at each time point derived from groups of individual mice. In some instances, the error bars are small and contained within the symbol. The delay in gastric emptying observed in response to increased caloric content is consistent with known gastric physiology and is preserved in nNOS^–/– mice. (c) EFS-evoked NANC relaxations were monitored from wild-type and nNOS^–/– pylori as described (see Methods). After precontraction with SP (0.1 μM), wild-type pylori demonstrate relaxation (> 95%) in response to EFS (40 V, 10 Hz, 5 ms pulse for a duration of 5 seconds), whereas relaxation is nearly absent in nNOS^–/– pylori (< 5%). All EFS-evoked relaxations were blocked with 0.1 μM TTX and the nNOS inhibitors L-NNA (0.1 mM) and 7-NI (0.1 mM). The examples shown are from a representative experiment. (d) Quantification of NANC-induced relaxations in response to EFS for wild-type and nNOS^–/– pylori. Several pylori representing wild-type and nNOS^–/– mice were used to quantitatively analyze the degree of NANC relaxation in response to EFS. Data shown are the means (± SEM) of several determinations for each group of mice (n = 20 for wild-type and 10 for nNOS^–/– pylori). ^AP < 0.01 compared with wild-type specimens.