Effects of maternal calorie-restricted diet on development of the foetal heart, as evaluated in primary cultures of rat myocardial cells.
Very-low-calorie diets have been implicated in causing ventricular arrhythmias and sudden cardiac death. Furthermore, studies indicate that maternal carbohydrate-restricted diets consumed during pregnancy and lactation reduce foetal growth, parturition and postnatal survival of rat pups. In this study, Sprague-Dawley rats were maintained on a semi-purified full-calorie or 50% carbohydrate-calorie-restricted diet throughout pregnancy. The function and integrity of myocardial cell cultures obtained from 3-5-day-old offspring from both groups of dams were evaluated after a drug-induced toxic challenge. After the myocytes had been in culture for 4 days, they were exposed to various concentrations of amitriptyline (1 x 10(-3) to 1 x 10(-5) M). Morphology, beating activity, lactate dehydrogenase release, glucose utilization, beta-adrenergic receptor [125I]iodopindolol binding, and cellular adenosine triphosphate content were evaluated for 24 hr after drug exposure. There were no significant differences in morphology, beating activity or glucose utilization between the full-calorie and calorie-restricted groups. When compared with the full-calorie group, lactate dehydrogenase release from the calorie-restricted group was significantly lower at 8 hr for the untreated controls and those cells exposed to 1 x 10(-4) and 1 x 10(-5) M-amitriptyline. Adenosine triphosphate levels were lower in untreated controls from the calorie-restricted group when compared with the full-calorie group at 4 hr. Within the calorie-restricted group, those cultures exposed to 1 x 10(-4) M-amitriptyline had significantly depressed adenosine triphosphate levels after 8 hr of drug treatment when compared with their respective untreated controls. Finally, the calorie-restricted group had significantly increased binding affinities of beta-receptors. Thus, maternal consumption of calorie-restricted diets during pregnancy may affect the myocardial functional capacity and integrity of the offspring.
Welder
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AA
College of Pharmacy, University of Oklahoma Health Sciences Center, Division of Medicinal Chemistry and Pharmacodynamics, Oklahoma City 73190.
Grant
R
R
Kutschke
R L
RL
Anthony
M
M
Bradlaw
J
J
Acosta
D
D
D000255:Adenosine Triphosphate / Q000032:analysis; D000639:Amitriptyline / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004038:Diet, Reducing / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D002149:Energy Intake; D005260:Female; D005318:Fetal Heart / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D006340:Heart Rate, Fetal / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D004040:Dietary Carbohydrates; D011943:Receptors, Adrenergic, beta; D000639:Amitriptyline; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase