Cerebrovascular dilatory and protective effects of VIP in newborn piglets

Abstract

VIP dilates cerebral vessels and is protective against ischemic brain damage, but the mechanisms of these actions have not been investigated in the newborn. VIP and pituitary adenylate cyclase activating polypeptide (PACAP) are structurally related neurotransmitters potentially acting on common receptors. We tested if 1) VIP‐induced cerebral vasodilation is mediated by a) cyclooxygenase (COX), b) nitric oxide synthase (NOS) or c) PACAP‐receptors; 2) VIP preserves cerebrovascular responsiveness after I/R. Pial arteriolar diameter was measured by intravital microscopy in newborn piglets equipped with closed cranial windows. VIP (10−9−10−6M) caused a significant, dose‐dependent pial arteriolar dilation that was blocked by the non‐selective COX‐inhibitor, indomethacin, only at 10−9−10−8M VIP, was unaffected by the NOS inhibitor, L‐NAME, and reduced by the PACAP antagonists, PACAP 6–27 and 6–38. VIP (10−9M, 20 min before I/R) preserved the endothelium‐dependent response to hypercapnia, but not the neuronal‐dependent reactivity to NMDA. We conclude that 1) vasodilator effect of VIP partially involves COX and common receptors with PACAP and 2) VIP protects cerebrovascular endothelial function against I/R. Supported by the Hungarian Scientific Research Fund (OTKA K63401 and K68976) and the Hungarian Health Science Board (ETT 194042006).