Cutaneous vascular permeability factors (histamine, 5-hydroxytryptamine, bradykinin) and passive cutaneous anaphylaxis in sheep

Abstract The cutaneous blood vessels of sheep are more sensitive to histamine than those of laboratory rodents. The threshold dose in sheep was 0·0025 μg histamine. The ovine vessels are 70 to 100 times less sensitive to 5-hydroxytryptamine (5-HT) than to histamine, but only four times less sensitive to bradykinin than to histamine. The effects of compound 48/80 are antagonized both by the antihistamine agent mepyramine and by the anti-5-HT agent methysergide, which suggests that compound 48/80 may release 5-HT in addition to histamine in sheep. The capillary-damaging effects of passive cutaneous anaphylaxis in sheep are antagonized by methysergide and by sodium meclofenamate—an agent which antagonizes kinins and slow-reacting substance. The antihistamine agent mepyramine has a small anti-anaphylactic effect, whereas promethazine—a less specific antihistamine—offers more protection to the blood vessels against local anaphylaxis. It is concluded that in the complex interaction of chemical mediators of anaphylaxis in the cutaneous blood vessels of sheep, 5-HT and kinin (and/or SRS-A) may be more important than histamine.