Vascular changes in rabbit skin induced by proinflammatory phorbol and 12-deoxyphorbol esters

The effects of proinflammatory phorbol and 12-deoxyphorbol esters were determined on blood flow changes and plasma exudation in rabbit skin. Blood flow changes were measured by means of¹³³Xe washout over that in control-treated sites, while plasma exudation was measured by¹³¹I-labeled human serum albumin leakage from skin blood vessels. 12-Deoxyphorbol-13-phenylacetate, 12-deoxyphorbol-13-angelate, and their C-20 acetates induced vasoconstriction in rabbit skin in doses of 100 ng/site. Tetradecanoyl phorbol acetate induced vasoconstriction to a far lower degree, while the parent alcohol phorbol and 9,13,14-orthophenylacetyl-resiniferonol had no significant effects on rabbit microvasculature. The ability of tigliane esters to contract rabbit blood vessels was confirmed in vitro in that each of these esters induced a prolonged contraction of superfused rabbit aorta in doses of 1–5g. Plasma exudation in rabbit skin was not significantly increased by the phorbol and 12-deoxyphorbol esters, but in a second determination using 100 ng of PGE₁ together with 100 ng of ester, plasma exudations of up to 40l per site were recorded.