Enhancement Of The Effect Of Bradykinin On Microvascular Permeability By A Peptide Derived From Fibrinogen

Abstract

Some low molecular weight fibrin degradation products (LMW-FDP) cause increased microvascular leakage in the dorsal skin of the rat. Two peptides earlier termed 6A and 6D seem to cause most of this effect. As unfractioned LMW-FDP potentiate bradykinin we have investigated how the leakage due to bradykinin is affected by the peptides 6A and 6DMethods. Different concentrations of peptide 6A (Ala-Arg- Pro-Ala-Lys), 6D (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys), inhibitors of kininase I and II (arginine and SQ14,225) were tested alone as well as together with different concentrations of bradykinin. The substances were injected in the previously shaved dorsal skin of 125I-albumin treated rats. The radioactivity content in the skin was measured in each injection site and the effect on microvascular permeability was calculated.Results. Thirty minutes after an injection of 6A or SQ14,225 together with bradykinin the leakage due to each mixture was greater than the sum of each substance per se. The response was dose-dependant. Simultaneous application of 6A, bradykinin and SQ14,225 caused a further increase in microvascular permeability. 6A and arginine had only marginal action upon the leakage due to bradykinin. 6A did not potentiate the effect of bradykinin after 5 min, while SQ14,225 showed a slight potentiation, however less than after 30 min. SQ14,225 itself was without effect.Discussion. As peptide 6A did not potentiate bradykinin after 5 min in contradiction to SQ14,225 it seems that their effects are not completely identical. The dramatical effect of SQ14,225 and the limited effect of arginine indicate that kininase II is the principle enzyme degrading bradykinin in rat skin. The effect of peptide 6A, even at low concentrations, indicate that this peptide, apart from its intrinsic effect on microvascular permeability, also can be of pathophysiologic significance in inflammatory states as potentiator of bradykinin.