Differing effects of histamine and serotonin on microvascular permeability in anaesthetized rats

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Abstract
We have investigated simultaneous changes in the hydraulic permeability (Lp) and the retention of perfusate macromolecules in single mesenteric venules of anaesthetized rats during perfusion with either histamine or serotonin. The venules were microperfused in situ. Retention of macromolecules was assessed from the effective oncotic pressure (σΔπ) exerted by the perfusate across the vessel walls. Lp and σΔπ were estimated by the red cell microperfusion technique. Perfusion with histamine (at concentrations between 16 μm and 3.26 mm) and serotonin (at concentrations between 26 μm and 1.3 mm) transiently increased Lp and reduced σΔπ Maximal changes were seen at 6–9 min with histamine and at 3 min with serotonin. Maximal increases in Lp were greater with histamine (approximately 3 ‐fold) than with serotonin (1.5‐ to 2‐fold). Serotonin, however, decreased σΔπ from a baseline of 14–15 cm H2O to one of 6–7 cm H2O whereas the fall of σΔπ with histamine was only from 14–15 cm H2O to 10–11 cm H2O. The data are consistent with the hypothesis that serotonin increases permeability by inducing openings in the venular endothelium which do not retain macromolecules. If histamine also increases permeability by gap formation, these gaps are able to retain macromolecules to a significant extent.