Circulatory and metabolic effects of alpha-adrenergic blockade in the hyperinsulinemic ovine fetus.
OBJECTIVE
Fetuses of diabetic women exhibit hypoxemia, elevated catecholamine concentrations at birth, and increased incidence of death. Our previous findings suggested that experimental fetal hyperinsulinemia results in a surge in catecholamines with cardiovascular changes supported by increased beta-adrenergic activity. The present experiments were designed to assess the contribution of alpha-adrenergic stimulation to the hemodynamic changes in the hyperinsulinemic ovine fetus.


METHODS
Combined ventricular output, regional organ blood flow, vascular resistance, metabolism, and catecholamine concentrations were measured before and during an infusion of insulin and during continued infusion with alpha-adrenergic blockade (phentolamine) in eight chronically catheterized fetal sheep.


RESULTS
Fetal insulin infusion produced hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increases in the combined ventricular output (blood flow to the fetus plus placenta) and regional blood flow to the fetus, heart, stomach, gastrointestinal tract, fat, and carcass. In the hyperinsulinemic state, alpha-adrenergic blockade was associated with additional increases in fetal norepinephrine concentration and no major changes in combined ventricular output or blood flow to the body of the fetus, except for decreased blood flow to the stomach and lungs, and a decrease in stroke volume.


CONCLUSIONS
Because vasodilation characterizes the hyperinsulinemic state, alpha-adrenergic stimulation contributes less to compensatory cardiovascular changes in the hyperinsulinemic fetus than that which we previously have shown for beta-adrenergic stimulation.
Stonestreet
B S
BS
Department of Pediatrics, Women & Infants' Hospital of Rhode Island, Brown University School of Medicine, Providence, Rhode Island 02905, USA.
Boyle
L D
LD
Papparella
A
A
Berard
D J
DJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005333:Fetus / Q000098:blood supply* / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D008168:Lung / Q000098:blood supply / Q000196:embryology; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D011247:Pregnancy; D012756:Sheep; D013270:Stomach / Q000098:blood supply / Q000196:embryology; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine