Vascular reactions to histamine, histamine‐liberator and leukotaxine in the skin of guinea‐pigs

Abstract

A substantial increase in capillary permeability is a feature of acute inflammation in bacterial infections. The present investigation is part of an attempt to prove an old hypothesis, namely, that this increase in permeability is mediated by histamine. A comparative study was made of histamine, of the histamineliberator 48/80, a condensation product ofp-methoxyphenylethylmethylamine and formaldehyde (Baltzly, Buck, de Beer & Webb, 1949), and of leukotaxine (Menkin, 1936(Menkin, , 1938a.In animals with a recently injected vital dye in their blood, the intradermal injection of substances that increase permeability of the blood vessels is followed by an accumulation of dye at the site of injection, presumably due to the passage of an excess of dye-stained plasma into the tissue spaces. When the blood flow and the vascular bed of the skin are relatively constant, differences in the size and intensity of stained areas of skin reflect differences in vascular permeability, and may be used to investigate the properties of substances that increase permeability in this way. Our work was confined to the skin of guinea-pigs, partly because much is already known about skin reactions to toxins and other inflammatory agents, and partly because it is a tissue readily studied in the intact and unanaesthetized animal-an important consideration with phenomena which, like the passage of dye through vascular endothelium, are peculiarly dependent on the state of the blood vessels in the tissue under test. MATERIALS AND METHODSAlbino guinea-pigs, 300-450 g in weight, were used throughout. The skin of the trunk was depilated, after clipping away the hair, by a paste consisting of wheat flour, 350 g; talcum powder, 350 g; barium sulphide, 250 g; Castile soap powder, 50 g; and water. The depilated area was thoroughly washed with warm water.Detection of increawed permeability. Neither the intradermal injection nor the pricking-in of histamine or 48/80 produce in the depilated skin any measurable reaction indicating change in

The induction of plasma leakage in skin by histamine, bradykinin, activated complement, platelet‐activating factor and serotonin

“…Substance P, a neurotransmitter which induces mast cell degranulation in some species (16), lacked activity as a mediator of enhanced permeability in sheep as has been reported in rabbits (17). The time course ofplasma leakage induced by histamine and bradykinin was similar to that reported in man (18), guinea-pigs (19) and rabbits (20). Platelet-activating factor showed a similar early peak in plasma leakage, however, in contrast to histamine and bradykinin, plasma leakage continued at an appreciable rate in the interval from 30-40 min.…”

Action of Compound 48/80 on the Mast Cells and Histamine Content of Guinea‐pig Tissues

“…Feldberg and Miles (1953) injected compound 48/80 intravenously in guinea-pigs previously injected with pontamine blue, and observed that different areas of the skin were blued in proportion to their histamine content. Miles and Miles (1952) using the same stain showed intensified blueing of the cutaneous area injected with compound 48/80. This phenomenon was considered to be an effect of the released histamine since it was antagonized by mepyramine.…”

Targeted therapy of orthotopic human lung cancer by combined vascular endothelial growth factor and epidermal growth factor receptor signaling blockade

“…3A and B). To complement the angiogenesis assay, we also examined the effect of ZD6474 treatment upon vascular permeability in vivo using the Miles assay (30). Treatment of mice with ZD6474 decreased the vascular permeability induced by CM, VEGF, or EGF.…”