Endoluminal substance P as a cause of mucosal hyperemia in the feline gut by a nonneural mechanism

Exogenous substance P (SP) was perfused into the lumen of the proximal jejunum in 16 fasted cats at a rate of 6.04 ± 1.96 ng/min. Regional blood flow was measured by radioactive microspheres after successive 15-minute perfusions with saline (basal), neural blockers, SP, and saline. Endoluminal SP caused mucosal hyperemia in the perfused jejunal segment that was not blocked by preperfusion of the segment with lidocaine (2% or 4%) or tetrodotoxin (3 × 10^-7 M). In addition, there was no increase in blood flow to any other organ tested, gastrointestinal or systemic. Local luminal SP levels rose but there was no significant rise in portal SP levels, indicating that the peptide was not absorbed. The data suggest that SP acts locally by a nonneural mechanism to influence local gastrointestinal blood flow.