All D-VIP mitigates vasodilation elicited by L-VIP, micellar L-VIP and micellar PACAP1-38, but not PACAP1-38, in vivo

The purpose of this study was to determine whether all D-vasoactive intestinal peptide (VIP), an inactive optical isomer of L-VIP, modulates the vasorelaxant effects of human L-VIP and pituitary adenylate cyclase activating peptide (PACAP)1-38, two ubiquitous and pleiotropic neuropeptides that activate VPAC1 and VPAC2, two VIP subtype receptors, in the intact peripheral microcirculation. Using intravital microscopy, we found that suffusion of all D-VIP had no significant effects on arteriolar diameter in the intact hamster cheek pouch. However, all D-VIP significantly attenuated L-VIP-induced vasodilation in a concentration-dependent fashion (P<0.05). likewise, all D-VIP significantly attenuated the vasorelaxant effects of L-VIP associated with sterically stabilized phospholipid micelles (SSM; P<0.05). Although all D-VIP had no significant effects on L-PACAP1-38-induced vasodilation, it abrogated PACAP1-38 in SSM-induced responses (P<0.05). The effects of all D-VIP were specific because it had no significant effects on acetylcholine-, nitroglycerin- and bradykinin-induced vasodilation. Taken together, these data indicate that all D-VIP attenuates the vasorelaxant effects of random coil and alpha-helix L-VIP as well as those of alpha-helix but not random coil PACAP in the intact peripheral microcirculation in a specific fashion. These effects are mediated, most likely, through interactions with VPAC1/VPAC2 receptors. We suggest that all D-VIP could be exploited as a novel, safe and active targeting moiety of VPAC1/VPAC2 receptors in vivo.