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BACKGROUND AND AIMS: We anylazed expression of substance P (SP) and nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric hydrochloric acid infusion. METHODS: The study was performed on 8 immature gilts of the Large White Polish breed. All animals were injected retrograde neuronal marker Fast Blue (FB) into the anterior prepyloric stomach wall and then divided into 2 groups (n=4 each). On 23rd day after FB injection gilts of the HCL group received single infusion of hydrochloric acid into the stomach. On 28th day all control and HCL pigs were euthanized and bilateral right (rNG) and left (lNG) were collected. Cryostat sections were processed for double immunofluorescence using antibodies against SP and NOS. RESULTS: Immunofluorescence staining of the nodose ganglia in control group showed the presence of FB-positive (gastric) neurons expressing SP (45.9±3.38% in rNG and 60.4±1.71% in lNG) and NOS (34.9±6.83% in rNG and 49.9±9.32% in lNG). The SPpositive neurons revealed granular immunoreaction product evenly distributed throughout the cytoplasm. The NOS immunostaining appeared as smooth immunoprecipitate observed throughout the cytoplasm. In HCL group increased expression of SP in the rNG (54.8±5.34%) and decreased in lNG (56.9±3.28%) was found in gastric neurons. While number of FB+/NOS-immunoreactive perikarya increased in both rNG (54.9±4.45%) and lNG (52.5±2.17%) respectively. Both appearance as well as distribution of immunoreaction products resembled that in control group. CONCLUSIONS: The acquired results suggest that SP and NOS function as neurotransmitters/neuromodulators in the vagal sensory transduction from prepyloric region of the porcine stomach. Additionally, they are possibly involved in pathological changes related to hyperacidity induced gastritis.