On the Mechanism of Vascular Leakage Caused by Histamine-Type Mediators

A current hypothesis maintains that the vascular leakage induced by histamine, serotonin, and bradykinin is brought about by a hydrostatic mechanism: The larger veins are said to contract; the venules are therefore submitted to an increase in pressure, which causes their wall to give way. To test this hypothesis, vessels of an exposed striated muscle (rat and rabbit cremaster) were photographed while treated with the above-mentioned substances; the occurrence of vascular leakage was tested by the intravenous injection of carbon black (carbon labeling). All animals were under barbiturate anesthesia, given a neuromuscular blocking agent (gallamine triethiodid), and were maintained by artificial respiration, according to a technique previously described. In 72 rats and 4 rabbits, the first event observed was arteriolar dilatation. Constriction of a small vein was observed in only 1 in 76 experiments (in two other cases it was doubtful). It is concluded that venous spasm cannot account for the leakage induced by the mediators of the histamine type, though such leakage may be enhanced by venous spasm whenever it may occur. An alternative mechanism is proposed and discussed: Histamine-type mediators cause vascular leakage by a direct effect on the venular endothelium, which is induced to contract.