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

1. 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. 2. The venules were microperfused in situ. Retention of macromolecules was assessed from the effective oncotic pressure (omega delta pi) exerted by the perfusate across the vessel walls. Lp and omega delta pi were estimated by the red cell microperfusion technique. 3. Perfusion with histamine (at concentrations between 16 microM and 3.26 mM) and serotonin (at concentrations between 26 microM and 1.3 mM) transiently increased Lp and reduced omega delta pi. Maximal changes were seen at 6-9 min with histamine and at 3 min with serotonin. 4. Maximal increases in Lp were greater with histamine (approximately 3-fold) than with serotonin (1.5- to 2-fold). Serotonin, however, decreased omega delta pi from a baseline of 14-15 cmH2O to one of 6-7 cmH2O whereas the fall of omega delta pi with histamine was only from 14-15 cmH2O to 10-11 cmH2O. 5. 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.