Carbazochrome sodium sulfonate (AC-17) reverses endothelial barrier dysfunction through inhibition of phosphatidylinositol hydrolysis in cultured porcine endothelial cells.

The effect of carbazochrome sodium sulfonate (AC-17), a hemostatic drug with capillary stabilising action, on the endothelial barrier dysfunction induced by a variety of vasoactive substances or agents that increase the vascular permeability was investigated in the monolayers of cultured porcine aortic endothelial cells (PAECs). The endothelial barrier function was determined by the transendothelial transport of albumin-conjugated Evans blue. AC-17 (0.1-1 M) reversed the barrier dysfunction induced by tryptase, thrombin and bradykinin without affecting the endothelial permeability enhanced by Ca(2+) ionophores such as ionomycin and A23187 or phorbol 12-myristate 13-acetate. Immunofluorescence analysis showed that AC-17 reversed the tryptase-induced formation of actin stress fibres and disruption of VE-cadherin in PAECs. On the other hand, AC-17 (0.1-10 M) reduced concentration-dependently the enhancement of [(3)H]inositol triphosphate formation from [(3)H]myo-inositol induced by bradykinin and thrombin.Therefore, it is suggested that AC-17 reduces the vascular hyperpermeability induced by a variety of vasoactive agents through inhibition of agonist-induced phosphoinositide hydrolysis.