Developmental change in isoproterenol-mediated relaxation of pulmonary veins of fetal and newborn lambs.
beta-Adrenergic agonists are important regulators of perinatal pulmonary circulation. They cause vasodilation primarily via the adenyl cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) pathway. We examined the responses of isolated fourth-generation pulmonary veins of term fetal (145 +/- 2 days gestation) and newborn (10 +/- 1 days) lambs to isoproterenol, a beta-adrenergic agonist. In vessels preconstricted with U-46619 (a thromboxane A2 analog), isoproterenol induced greater relaxation in pulmonary veins of newborn lambs than in those of fetal lambs. The relaxation was eliminated by propranolol, a beta-adrenergic antagonist. Forskolin, an activator of adenyl cyclase, also caused greater relaxation of veins of newborn than those of fetal lambs. 8-Bromoadenosine 3',5'-cyclic monophosphate, a cell membrane-permeable analog of cAMP, induced a similar relaxation of all vessels. Biochemical studies 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-adrenergic-agonist-mediated relaxation of pulmonary veins increases with maturation. An increase in the activity of adenyl cyclase may contribute to the change.
Gao
Y
Y
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
Tolsa
J F
JF
Botello
M
M
Raj
J U
JU
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D005333:Fetus / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects; D012756:Sheep / Q000254:growth & development*
D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol