Characterization of vasopressin actions in isolated submucosal arterioles of the intestinal microcirculation

Submucosal arterioles are the final resistance vessels of the mesenteric circulation; they supply intestinal mucosa and smooth muscle and contribute significantly to total mesenteric resistance. Characterization of receptors present on submucosal arterioles has not been carried out, because these vessels have not been accessible to study by previous methods. We have used a novel optical method for on-line tracking of outside diameter from in vitro preparations of submucosal arterioles in the ileum and colon of guinea pigs, rabbits, and humans to characterize the vasoconstrictor responses to vasopressin as well as other vasopressor agents along the gastrointestinal tract. All ileal submucosal arterioles showed smoothly graded constrictor responses, whereas colonic arterioles from each species exhibited rhythmic vasoconstrictions. Vasopressin constricted guinea pig and human submucosal arterioles (EC50, 1 nM) by activating classical V1 receptors; dissociation equilibrium constants (Kd) for the V1 antagonist d(CH2)5 Tyr (Me) arginine vasopressin were 1-3 nM. This antagonist was 10-50-fold more potent in inhibiting vasopressin constrictions in rabbit submucosal arterioles (Kd = 0.05-0.1 nM). No evidence for the presence of V2 receptors was obtained in any arteriole, and no significant differences in the alpha 1-adrenoceptor-mediated constrictions were observed in these vessels. Results from this study suggest the presence of heterogeneity of V1 receptors in submucosal arterioles; these differences appear to be species dependent. Our results also suggest that intrinsic vasoconstrictor properties of submucosal arterioles differ along the length of the gastrointestinal tract; these differences appear to be species independent.