Sympathectomy and beta-adrenergic blockade during lung maturation stimulated by TRH and cortisol in fetal sheep.
To test whether beta-adrenergic mechanisms and the sympathetic nervous system are involved in the synergistic action of thyrotropin-releasing hormone (TRH) and cortisol on lung maturation, fetal sheep (n = 32) were infused from 121 to 128 days of gestation with saline, TRH + cortisol, TRH + cortisol + beta-adrenergic blocker, or TRH + cortisol after chemical sympathectomy with 6-hydroxydopamine. TRH + cortisol increased lung distensibility and stability and alveolar concentrations of saturated phosphatidylcholine two- to threefold over control fetuses. beta-Adrenergic blockade prevented the increase in distensibility in response to TRH + cortisol. Sympathectomy did not impair the increase in distensibility and stability in response to TRH + cortisol but inhibited the increase in alveolar total phospholipids. Tissue concentrations of saturated phosphatidylcholine increased in TRH + cortisol-treated fetuses after either sympathectomy or beta-adrenergic blockade. We concluded that during lung maturation by TRH + cortisol 1) sympathetic mechanisms are requisite for surfactant release, 2) nonneurogenic beta-adrenergic mechanisms are requisite for the maturation of the mechanical properties of the lung and 3) stimulation of surfactant synthesis is independent of beta-adrenergic action and the sympathetic nervous system.
Schellenberg
J C
JC
Department of Obstetrics and Gynaecology, University of Auckland, New Zealand.
Liggins
G C
GC
Kitterman
J A
JA
Lee
C C
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008168:Lung / Q000196:embryology*; D009929:Organ Size / Q000502:physiology; D016627:Oxidopamine; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D011247:Pregnancy; D012756:Sheep; D013563:Sympathectomy, Chemical; D013973:Thyrotropin-Releasing Hormone / Q000097:blood / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001798:Blood Proteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D013973:Thyrotropin-Releasing Hormone; D016627:Oxidopamine; D004247:DNA; D006854:Hydrocortisone