ANTENATAL BETAMETHASONE THERAPY AUGMENTS ISOPROTERENOL AND PROSTAGLANDIN E-2-MEDIATED RELAXATION OF PRETERM OVINE PULMONARY VEINS

Antenatal glucocorticoid therapy improves pulmonary function in preter m newborns. We have determined the effect of antenatal glucocorticoid therapy on isoproterenol and prostaglandin (PG) E-2-mediated relaxatio n in preterm ovine pulmonary veins after birth. Ovine fetuses (121 and 126 d of gestation; term = 150 d) received an ultrasound guided intra muscular injection of betamethasone, 0.5 mg/kg, or saline. Lambs were delivered 15 or 48 h later, ventilated for 3 h, and killed. Isolated f ourth generation pulmonary veins were suspended in organ chambers fill ed with modified Krebs-Ringer solution (95% O-2, 5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to U 46619, isoproterenol and PGE(2) induced greater relaxations of pulmona ry veins of betamethasone-treated lambs than those of control. Forskol in, an activator of adenylate cyclase, caused greater relaxation in ve ins of betamethasone-treated lambs than in those of controls. A greate r relaxation of veins treated with betamethasone than that of control veins also occurred in the presence of isobutylmethylxanthine, an inhi bitor of phosphodiesterases. All vessels relaxed similarly to 8-bromo- cAMP, a cell membrane-permeable analog of cAMP. When stimulated with i soproterenol, PGE(2), and forskolin, adenylate cyclase activity of cru de membrane preparations of pulmonary veins treated with betamethasone was greater than that of controls, These results demonstrate that ant enatal betamethasone therapy potentiates isoproterenol and PGE(2)-medi ated relaxation of pulmonary veins of preterm lambs; an enhanced adeny late cyclase activity explain in part the effect of antenatal glucocor ticoid therapy on pulmonary veins of preterm lambs.