Effects of beraprost sodium (a PGI2 derivative) on chronic hypoxic pulmonary hypertension in the rat

Abstract

To determine whether beraprost sodium (beraprost) can cause pulmonary vasodilation in chronic hypoxic pulmonary hypertension, we measured the hemodynamic effects of intravenous beraprost, a stable and orally active agent with a PGI2-like structure, in chronic hypoxic (H) and normoxic (N) rats. During anesthesia baseline pulmonary artery pressure (PAP) was 32.0 +/- 1.0 in H rats and 18.0 +/- 0.4 mmHg in N rats. Intravenous beraprost (20 micrograms/kg) elicited acute pulmonary vasodilation by 17.7 +/- 4.6% (5.6 +/- 1.4 mmHg) in H rats and by 16.8 +/- 2.1% (3.0 +/- 0.6 mmHg) in N rats, which indicates that the relative degree of acute pulmonary vasodilation caused by beraprost was similar in H and N rats. Thirty minutes after the drug was injected, PAP had not returned to baseline levels in either H or N rats, and it was lower in H rats (90 +/- 2%) than in N rats (95 +/- 2%). Lungs were isolated and perfused with saline, and those from H rats and N rats showed similar pulmonary vasodilator responses to 2 and 20 micrograms/kg beraprost. These results indicate that although beraprost caused a similar degree of acute pulmonary vasodilation in H and N rats, in H rats the response lasted longer. Thus PGI2 derivatives may be useful as vasodilators in some patients with primary and secondary pulmonary hypertension.