Tissue differences in vascular permeability changes induced by histamine.

A new method is described for assessing changes in vascular permeation by albumin in multiple tissues of the same animal in response to intravascular injection of vasoactive agents. Following intravenous injection of 51Cr-RBC, 125I-BSA, and 57Co-EDTA, a test substance (i.e., histamine) is injected intravascularly or subcutaneously. Eight minutes later approximately 2.0 ml of blood is withdrawn and the heart is severed from the great vessels. Samples of tissue are then taken for determination of water content and for the ratio of counts in 125I and 51Cr in each tissue. That ratio is then divided by the corresponding ratio of the same isotopes in the blood. If the resulting quotient is greater than 1, it indicates that the volume of distribution of 125I in the tissues is greater than the ratio of plasma to red cells in large blood vessels and is indicative of permeation of the vasculature by albumin into the extravascular space. With this technique we have demonstrated that following intravenous injection of histamine, albumin permeation of vessels in the cecum is increased much more than for vessels in any other tissue in the body including skin and muscle. Following intravenous injection of 1.5 mg/kg histamine, albumin permeation in the cecum is increased 4-fold while that in skin is unchanged, except at sites where histamine also has been injected subcutaneously where it is increased 1.7-fold by 3 microgram and 10-fold by 15 micrograms of histamine. The magnitude of increases in albumin permeation of the vasculature after intravenous injection of 7.5 mg/kg of histamine was: cecum--5.1 X greater than pancreas--2.8 X greater than small intestine--2.7 X greater than cremaster and stomach--2.0 X greater than eye and aorta--1.9 X greater than fat--1.7 X greater than skin--1.6 X greater than diaphragm and forelimb--1.5 X. Even at this high dose of histamine, tissue to blood isotope ratio (tbir)-I/Cr values were not increased for heart, brain, kidney, lung, or testis. These findings attest to marked tissue differences in sensitivity to histamine-induced changes in vascular permeation by albumin. The additional that histamine-induced tbir-I/Cr increases in most tissues far exceed tbir-Co/Cr increases indicates that the increase in albumin permeation of vessels is mediated in large part by an increased rate of diffusion (rather than filtration) via an increase in the number and/or size of vascular pores large enough to accommodate albumin.