Effect of nitric oxide on substance P release from the peripheral endings of primary afferent neurons.

To elucidate the interaction between nitric oxide (NO) and substance P (SP) in neurogenic inflammatory responses, we studied the effect of drugs related to nitric oxide (NO) on the levels of Evans blue and SP released into perfusate from the subcutaneous space in the rat instep. Noxious heat stimulation (47 degrees C for 30 min) caused an increase in SP release in parallel with plasma extravagation. N(omega)-nitro-L-arginine methylester (L-NAME: 100 mg/kg, once daily) given intraperitoneally (i.p.) five times (chronic treatment) significantly suppressed the heat-evoked SP release and Evans blue leakage. FK409 (10(-4) M), which evokes a release of NO, applied locally caused a remarkable increase in the SP release into the perfusate. These results suggest that heat-induced NO generation causes SP release from the peripheral endings of small-diameter primary afferent neurons.