Circulatory and metabolic effects of beta-adrenergic blockade in the hyperinsulinemic ovine fetus.
Offspring of women with poorly controlled diabetes exhibit hypoxemia, elevated catecholamine concentration at birth, and an increased incidence of fetal death. Experimental fetal hyperinsulinemia results in increased catecholamine concentration and hemodynamic changes including increased combined ventricular output and vasodilation of select fetal organs. We hypothesized that insulin-induced catecholamine-mediated beta-adrenergic stimulation supports some of these hemodynamic changes in the hyperinsulinemic ovine fetus. To study this, 24 chronically instrumented fetal sheep receiving insulin for 24 h were exposed to beta-(propranolol),beta 1-(metoprolol), and beta 2-(ICI 118,551) adrenergic blockade. Insulin infusion resulted in hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increases in the combined ventricular output and regional blood flow to the heart, adrenal glands, kidney, gastrointestinal tract, liver, fat, muscle, carcass, and placenta. In the hyperinsulinemic state, beta-adrenergic blockade was associated with significant reductions in the combined ventricular output and blood flow to fat, carcass, lungs, and the placenta; beta 1-blockade was associated with reductions in the combined ventricular output and blood flow to the lungs; and beta 2-adrenergic blockade was associated with reductions in blood flow to muscle and lungs. Because beta-adrenergic blockade was associated with reductions in placental blood flow during hyperinsulinemia, oxygen and glucose metabolism were also compromised. We conclude that in the hyperinsulinemic-hypoglycemic normoxemic ovine fetus, insulin-induced catecholamine-mediated hemodynamic changes are modulated in part by beta-adrenergic receptor stimulation.
Stonestreet
B S
BS
Brown University School of Medicine, Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Providence 02905.
Le
E
E
Berard
D J
DJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism / Q000503:physiopathology*; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D011247:Pregnancy; D012756:Sheep
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007328:Insulin