DIFFERING EFFECTS OF HISTAMINE AND SEROTONIN ON MICROVASCULAR PERMEABILITY IN ANESTHETIZED RATS

1. We have investigated simultaneous changes in the hydraulic permeabi lity (L-p) and the retention of perfusate macromolecules in single mes enteric venules of anaesthetized rats during perfusion with either his tamine or serotonin. 2. The venules were microperfused in situ. Retent ion of macromolecules was assessed from the effective oncotic pressure (sigma Delta pi) exerted by the perfusate across the vessel walls. L- p and sigma Delta pi were estimated by the red cell microperfusion tec hnique. 3. Perfusion with histamine (at concentrations between 16 mu M and 3.26 mM) and serotonin (at concentrations between 26 mu M and 1.3 mM) transiently increased L-p and reduced sigma Delta pi. Maximal cha nges were seen at 6-9 min with histamine and at 3 min with serotonin. 4. Maximal increases in L-p were greater with histamine (approximately 3-fold) than with serotonin (1.5- to 2-fold). Serotonin, however, dec reased sigma Delta pi from a baseline of 14-15 cmH(2)O to one of 6-7 c mH(2)O whereas the fall of sigma Delta pi with histamine was only from 14-15 cmH(2)O to 10-11 cmH(2)O.5. The data are consistent with the hy pothesis that serotonin increases permeability by inducing openings in the venular endothelium which do not retain macromolecules. If histam ine also increases permeability by gap formation, these gaps are able to retain macromolecules to a significant extent.