Daflon 500 mg depresses bradykinin-ischemia-induced microvascular leakage of FITC dextran in rat cremaster muscle.

Abstract

We studied the in vivo effects of Daflon 500 mg on transvascular movement of macromolecules induced by bradykinin (BK) and ischemia. The experimental preparation involved the rat cremaster muscle. The muscle was fashioned as a single bag (new procedure), placed in a transparent chamber and superfused with a bicarbonate buffer solution equilibrated with a 5% CO2 95% N2 gas mixture in order to obtain pH 7.40, PCO2 = 40 mmHg, PO2 = 20-40 mmHg and thermostated at 35 degrees C. FITC-Dextran 150 (MW 150,000) was injected i.v. as a macromolecular tracer. BK was added to the buffer solution at the concentration of 2 micrograms/ml five minutes after a control period of 60 minutes. Ischemia was performed during 60 min by a clamp positioned on the main artery of the cremaster muscle. Animals treated with Daflon 500 mg (100 mg/kg) 18 and 2 hours before experiments showed a significant reduction in FITC-Dextran 150 leakage in both BK and ischemia protocols. Leakage of FITC-Dextran 150 started 2-3 min after application of BK in the two animal groups but the response was less important (+ 270%) and the preparation returned to control appearance after 40 min in the treated rats in contrast with control rats (+ 450% and 70 min). The amplitude of FITC-Dextran 150 leakage was identical just one hour after ischemia in the two animal groups, but microvascular permeability returned to basal state in treated animals (30 min), a fact non observed in non treated animals. These data demonstrate the protective effect of Daflon 500 mg on the microvascular muscle network in vivo.