Effects of AVP and DDAVP on histamine-induced increases in macromolecular permeability in the hamster cheek pouch.

The effects of histamine alone and in the presence of AVP or DDAVP on microvascular permeability to macromolecules was evaluated in the superfused hamster cheek pouch. FITC-Dextran (MW 70,000) was employed as a macromolecular tracer to quantitate the increase in macromolecular permeability produced by the topical application of histamine. Intra-vital light microscopy was utilized to quantitate and localize FITC-D extravasation sites along the vascular tree, and fluorimetric measurement of the FITC-D concentration in the suffusate (S) and plasma (P) was used to calculate the FITC-D S/P ratio to quantitate the increase in macromolecular permeability. The infusion of histamine for 5 minutes at a rate which produced a suffusate histamine concentration of 1 X 10(-5) M produced a marked increase in the number of venular FITC-D leakage sites, the [FITC-D]s, and the FITC-D S/P ratio. These effects of histamine were prevented by treatment with either AVP or DDAVP which was infused at a rate sufficient to produce a suffusate concentration of 1 X 10(-8) M. AVP produced profound vasoconstriction whereas DDAVP prevented the histamine-induced increase in the formation of venular FITC-D leakage sites, the [FITC-D]s, and FITC-D S/P ratio without producing vasoconstriction. These data suggest that the antagonism of the histamine-induced increase in macromolecular permeability by AVP and DDAVP is not dependent on vasoconstriction per se, but rather is attributable to the stimulation of a vasopressin receptor on the venular endothelial cell which is identical to or similar to the vasopressin receptor mediating the anti-diuretic effects of these agents.