DEVELOPMENTAL-CHANGE IN ISOPROTERENOL-MEDIATED RELAXATION OF PULMONARY VEINS OF FETAL AND NEWBORN LAMBS

beta-Adrenergic agonists are important regulators of perinatal pulmona ry circulation. They cause vasodilation primarily via the adenyl cycla se-adenosine 3',5'-cyclic monophosphate (cAMP) pathway. We examined th e responses of isolated fourth-generation pulmonary veins of term feta l (145 +/- 2 days gestation) and newborn (10 +/- 1 days) lambs to isop roterenol, a beta-adrenergic agonist. In vessels preconstricted with U -46619 (a thromboxane A(2) analog), isoproterenol induced greater rela xation in pulmonary veins of newborn lambs than in those of fetal lamb s. The relaxation was eliminated by propranolol, a beta-adrenergic ant agonist. Forskolin, an activator of adenyl cyclase, also caused greate r relaxation of veins of newborn than those of fetal lambs. 8-Bromoade nosine 3',5'-cyclic monophosphate, a cell membrane-permeable analog of cAMP, induced a similar relaxation of all vessels. Biochemical studie s show that isoproterenol and forskolin induced a greater increase in cAMP content and in adenyl cyclase activity of pulmonary veins in the newborn than in the fetal lamb. These results demonstrate that beta-ad renergic-agonist-mediated relaxation of pulmonary veins increases with maturation. An increase in the activity of adenyl cyclase may contrib ute to the change.