The glomerular polyanion (GPA) of the rat kidney. III. Further characterization of a vaso-active serum factor which reduces GPA.

Fractions of normal rat serum were purified using gel chromatography and their molecular weights were analysed using gradient polyacrylamide gel electrophoresis (PAGE). The fractions were tested for their capacity to affect in vitro glomerular polyanion (GPA) in rat kidney tissue whereas their vascular enhancing capacity in vivo after intradermal injection into the rat skin was analysed. GPA impairment in vitro was estimated after incubation of the fractions with tissue sections for 2 h at 37 degrees C and subsequent staining for sialoproteins with colloidal iron. Enhanced vascular responses were assayed using a standard vascular permeability test in the rat skin. The results show that a factor with an estimated molecular weight of 120 000 was responsible for a dose-related activity in both test systems studied. The activity of this fraction could be inhibited by various plasma kallikrein-inhibiting protease inhibitors, whereas in addition the skin response could be inhibited by pyridinolcarbamate and not by histamine- or serotonin-inhibiting drugs. From the inhibition patterns in vivo and in vitro as well as from the estimated molecular weight of the fraction, it is suggested that a plasma kallikrein-like factor might be responsible for the activities observed. We feel that further study of this fraction in rat or human serum is worthwhile in particular with respect to nephrotic conditions associated with GPA loss.