Angiotensin converting enzyme dependent and non-dependent effects of a fibrinogen-derived pentapeptide on microvascular permeability in rat skin.

A permeability-increasing pentapeptide, termed peptide 6A, derived from plasmin-degraded human fibrinogen and known to potentiate the increase in microvascular permeability caused by bradykinin was investigated concerning its angiotensin converting enzyme (A.C.E.) related effects. When applied to a rat skin model together with a specific inhibitor of this enzyme, peptide 6A showed a potentiated effect after 30 min. but not after 5 min. The same was also true for bradykinin. These findings suggest that the degradation rate of these peptides is decreased with resulting prolongation of the period of leakage, when the action of A.C.E. is opposed. It is deduced that peptide 6A may act as a partial antagonist of this enzyme in the rat skin model. Addition of peptide 6A to a mixture of bradykinin together with inhibitors of the enzymes degrading bradykinin before application to the rat skin, significantly augmented the extravasation of 125I-albumin. These findings are consistent with data indicating that peptide 6A is a prostacyclin-releaser able to induce vasodilation. This effect of peptide 6A on the microcirculation seems to be separate from its angiotensin converting enzyme-related effects.