Vasoactive intestinal polypeptide causes relaxation of the pyloric sphincter in the rabbit

Vasoactive intestinal peptide (VIP), which causes relaxation of gastrointestinal smooth muscle, has been found in high concentrations in the pylorus in many animal species, suggesting a prominent role for VIP in the control of pyloric sphincter function. We infused VIP into the gastric artery of 6 rabbits at rates from 12 to 1,200 ng/min and measured the intensity, duration, and frequency of spontaneous pyloric contractions with an intraluminal balloon and electromyography. VIP produced a dose-dependent reduction in the intensity (55% +/- 15% of baseline, P < .001) and the duration (29% +/- 25%, P < .001) of pyloric contraction. Maximal inhibition was observed at an infusion rate of 240 ng/min. The frequency of contractions did not decrease significantly in response to VIP infusion. Neostigmine infusion increased the intensity of pyloric contraction in a dose-dependent manner in doses of 0.10, 0.15, and 0.25 mg (140% +/- 78%, 273% +/- 76%, and 357% +/- 26% of baseline, respectively; P < .001). VIP infusion at 12 ng/min and 480 ng/min completely inhibited the increased intensity of contraction at neostigmine doses of 0.10 and 0.15 mg, respectively. Our results show that VIP decreases the intensity and the duration of pyloric contraction in a dose-dependent manner. As pyloric spasm may contribute to the pathogenesis of hypertrophic pyloric stenosis, we can postulate a role for reduced VIP-induced relaxation in the pathophysiology of hypertrophic pyloric stenosis.