Transient venular permeability increase and endothelial gap formation induced by histamine.

Histamine is known to increase permeability of venules and to cause formation of gaps between endothelial cells. The permeability increase is transient, lasting only a few minutes during continuous histamine application. In this study, three series of experiments were conducted to test the hypothesis that the transient permeability increase is due to transient formation of endothelial gaps. First, the time course of permeability changes to alpha-lactalbumin during 15 min of 10(-3) M histamine suffusion was determined on single venules in the rat mesentery. With histamine application, permeability increased initially, peaked with an average of fivefold increase around the 3rd min, and then declined toward control. Second, the temporal development of endothelial gaps during histamine treatment was studied with electron microscopy. The fraction of gaps among all junctions increased from 2% at control to 26.5% at 3 min and then decreased toward control. Finally, gap morphology data were obtained from the individual venules whose permeability response to a given period of histamine treatment had been recorded. The temporal development of the gaps was mirrored by that of permeability. Because both permeability and endothelial gaps followed similar developmental patterns during histamine treatment, the result of our study supports the hypothesis that the histamine-induced transient permeability increase is due to transient formation of endothelial gaps.