MECHANISMS OF VASODILATION ELICITED BY VIP IN STERICALLY STABILIZED LIPOSOMES IN-VIVO

Mechanisms of vasodilation elicited by VIP in sterically stabilized li posomes in vivo. Am. J. Physiol. 273 (Regulatory Integrative Comp. Phy siol. 42): R287-R292, 1997.-The purpose of this study was to begin to determine the mechanisms underlying vasodilation elicited by vasoactiv e intestinal peptide (VIP) in sterically stabilized Liposomes (SSL) in the in situ peripheral microcirculation. Using intravital microscopy, we found that suffusion of VIP in SSL (0.42 and 0.85 nmol) onto the h amster cheek pouch for 1 h elicited significant and prolonged concentr ation-dependent vasodilation (P < 0.05). Suffusion of VIP in SSL (0.1 nmol) for 7 min elicited a qualitatively similar response, although it s magnitude was significantly smaller than that elicited by 1 h of suf fusion of VIP in SSL (P < 0.05). The VIP-receptor antagonist VIP-(10-2 8), but not the amino-terminal fragment VIP-(1-12), significantly atte nuated and delayed the onset of VIP in SSL-induced vasodilation (P < 0 .05). The nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine me thyl ester (L-NAME), but not N-G-nitro-D-arginine methyl ester (D-NAME ), abrogated VIP in SSL-induced responses. We conclude that VIP in SSL elicits significant and prolonged vasodilation in the in situ periphe ral microcirculation, which is specific, partly receptor dependent, an d partly transduced by the L-arginine/NO biosynthetic pathway.