Ys. Gao et al., DEVELOPMENTAL-CHANGE IN ISOPROTERENOL-MEDIATED RELAXATION OF PULMONARY VEINS OF FETAL AND NEWBORN LAMBS, Journal of applied physiology, 84(5), 1998, pp. 1535-1539
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.