Mucosal stimulation evokes vasodilation in submucosal arterioles by neuronal and nonneuronal mechanisms

The effects of mechanical stimulation of intestinal mucosa on submucosal arterioles of guinea pig ileum were examined using video microscopy of in vitro preparations consisting of submucosal plexus with adjacently attached mucosa. Mucosal stimulation did not alter the diameter of relaxed vessels but dilated arterioles preconstricted with phenylephrine or the prostaglandin analogue U-46619. Tetrodotoxin (TTX) or muscarinic receptor antagonists inhibited the vasodilation evoked by mucosal stimulation in 60% of preparations examined from normal and extrinsically denervated animals. The TTX-sensitive vasodilation to mucosa stimulation was partially inhibited by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205930. The TTX-insensitive vasodilation was largely prevented when the histamine receptor antagonists cimetidine and pyrilamine and the prostaglandin synthesis inhibitor indomethacin were applied. This study has demonstrated a reflex vasodilation to mucosal stimulation in an isolated submucosal plexus preparation that involves both neuronal and nonneuronal pathways. The neuronal pathway converges on cholinergic vasodilator neurons in the submucosal ganglia. The nonneuronal pathway involves the release of 5-HT, histamine, and prostaglandins from mucosal elements; 5-HT excites cholinergic vasodilator neurons, whereas histamine and prostaglandins dilate submucosal arterioles directly.