Anti-Inflammatory Effects of Beraprost Sodium, a Stable Analogue of PGI2, and Its Mechanisms

We examined whether beraprost sodium (beraprost), a stable analogue of PGI₂, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 μg/head) plus epinephrine (0.6 μg/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 ± 1.64 μg/lung, beraprost 10 μg/kg; 7.49 ± 1.36 μg/lung, 30 μg/kg; 5.33 ± 0.71 μg/lung, 100 μg/kg; 5.52 ± 0.79 μg/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE₁ (170 μg/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 ± 0.01, control; 3.96 ± 0.04) and right ventricular hypertrophy (normal; 28.2 ± 0.9%, control; 32.3 ± 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 μg/kg/day of beraprost, the effects were statistically significant (beraprost 30 μg/kg/day; 3.85 ± 0.02 and 27.8 ± 1.4%, 100 μg/kg/day; 3.85 ± 0.02 and 27.3 ± 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10⁻¹³ mol/paw; 91.19 ± 2.22%, 10⁻¹² mol/paw; 85.79 ± 4.85%, 10⁻¹¹ mol/paw; 78.49 ± 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (−)-isoproterenol (10⁻¹² mol/paw), but PGE₁ (10⁻¹¹ mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo. © 1997 by Elsevier Science Inc.