Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by monocrotaline in rats.

The effect of administering prostaglandin E1 (PGE1) on the extent of monocrotaline (MCT)-induced pulmonary hypertension and cytokine production [interleukins (IL) 1 and 6 and tumor necrosis factor (TNF)] by macrophages during MCT induction of pulmonary hypertension was studied. Right ventricle/left ventricle plus septum weight ratios (RV/LV + S) were used as an index of the development of pulmonary hypertension. Administering PGE1 at a dose of 0.2 mg/kg/day for 4 weeks reduced significantly the RV/LV + S ratio from 0.428 +/- 0.070 to 0.243 +/- 0.059 (p < 0.01) and decreased the production of these cytokines: IL-1, from 4.675 +/- 3.558 to 1.800 +/- 0.722 units; IL-6, from 0.322 +/- 0.121 to 0.060 +/- 0.039 units; and TNF, from 0.578 +/- 0.369 to 0.004 +/- 0.004 units. In another series of experiments, a significant reduction of the RV/LV + S ratio was noted for only 1 week when we administered PGE1 immediately after the injection of MCT. We confirmed that histopathologic improvements of lungs were noted by administering 0. 2 mg/kg PGE1 for 4 weeks. In another experiment, PGE1 at a concentration of 2 microg/ml suppressed a rise in the cytosolic Ca2+ concentration of lipopolysaccharide-stimulated peritoneal macrophages of rats in vitro, suggesting that PGE1 suppressed cytokine production by macrophages through the suppression of the Ca2+ influx. These results suggest that administering PGE1 may be effective in the treatment of some forms of pulmonary hypertension in humans.