Does concurrent or prior nicotine exposure interact with neonatal hypoxia to produce cardiac cell damage?
Cigarette smoking during pregnancy exposes the fetus to both nicotine and hypoxia/ischemia; postnatal exposure to second-hand smoke also involves substances that cause hypoxia (CO, HCN). Although developing cardiac cells are more resistant to hypoxia-induced damage than are mature cells, we examined whether nicotine affects this resistance, either when exposure is concurrent with hypoxia, or when animals are exposed to nicotine prenatally and receive subsequent hypoxic exposure. One, 8-, or 15-day-old rats exposed to 7% O2 for 2 hr all showed inhibition of cardiac DNA synthesis. By contrast, administration of nicotine at either low (0.3 mg/kg) or high (3 mg/kg) doses failed to alter DNA synthesis. To examine effects on cells that were not undergoing mitosis, we examined ornithine decarboxylase (ODC), an enzymatic marker for cell damage. One day old rats showed inhibition of ODC by hypoxia, a response that represents preservation of cell integrity; by 8 days of age, ODC was increased by hypoxia, evidence of cell damage. The high dose of nicotine evoked an increase in ODC at all ages and the low dose exacerbated the effects of hypoxia at 8 days of age. Prenatal nicotine exposure caused a transient inhibition of cardiac DNA synthesis but did not produce evidence of cell damage (ODC, protein synthesis markers) by itself, nor did it alter the effect of a subsequent postnatal exposure to hypoxia. These results suggest that cardiac cell damage could emerge as a consequence of concurrent, repeated exposures to nicotine and hypoxia. Such effects could contribute to the elevated incidence of perinatal morbidity/mortality and Sudden Infant Death Syndrome associated with smoking.
Tolson
C M
CM
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Seidler
F J
FJ
McCook
E C
EC
Slotkin
T A
TA
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D011506:Proteins; D009538:Nicotine; D004247:DNA; D009955:Ornithine Decarboxylase