Increased permeability associated with dilatation of endothelial cell junctions caused by histamine in intimal explants from bovine pulmonary artery.

Although histamine is known to cause increased vascular permeability in the systemic circulation, its effect on the pulmonary vessels is controversial. We have used a new technique to follow the effect of histamine on the pulmonary artery endothelial cell layer. Disks of intima were stripped from the wall of bovine pulmonary artery, floated endothelium uppermost onto nitrocellulose filters, and maintained in culture in chemotaxis chambers. The lower well of the chambers contained 0.2 ml of 10% bovine serum in medium 199, the upper well 0.5 ml of medium plus trace amounts of 3H-water (10 microCi/ml), 14C-sucrose (9 microCi/ml), and 125I-albumin (10 microCi/ml). Histamine diphosphate (10 microM) was added to the upper well of the experimental chambers. The chambers were incubated at 37 degrees C for 30, 60, 120, 180, or 240 min. At the end of each incubation period, 0.1-ml aliquots were removed from the upper and lower well of an experimental and a control chamber for radioactive counts and the intimal explant was fixed in glutaraldehyde for light and electron microscopy. From 60 min of incubation, histamine caused more rapid equilibration of 3H-water and 14C-sucrose across the intimal explant. Increased diffusion of 125I-albumin was not detected. After 30 and 60 min of incubation with histamine, microscopic examination of the endothelial layer of the explant revealed focal dilatations in the intercellular junctions. From 120 min, dilatations were no longer seen and at no time was there morphologic evidence of endothelial injury. Thus, histamine causes an increased permeability of the bovine pulmonary artery intimal layer that is associated with transient formation of dilatations in the interendothelial junctions.