Prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion injury in adult offspring.
In the present study we tested the hypothesis that prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation. Nicotine treatment resulted in a rapid and transient decrease in food-intake and a moderate decrease in maternal body weight gain. Hearts were isolated from adult male and female offspring and subjected to I/R in a Langendorff preparation. Nicotine significantly attenuated left ventricle (LV) developed pressure, heart rate, and coronary flow rate in female but not male hearts at baseline. Additionally, nicotine significantly increased LV infarct size and attenuated postischemic recovery of LV function in both male and female offspring with more pronounced effects in females. In female but not male hearts, nicotine significantly decreased the postischemic coronary flow rate. However, coronary nitric oxide release was decreased in male but not female hearts. Caspase-3, -8, and -9 levels were not significantly changed in either female or male hearts. However, nicotine caused a significant decrease in protein levels of protein kinase (PK) Cepsilon in both male and female hearts and a decrease in PKCdelta levels in female hearts only. Control studies of maternal food restriction showed that a moderate decrease in maternal body weight gain had no effect on female hearts but significantly improved postischemic recovery of LV function in male hearts. The results suggest that prenatal nicotine exposure causes in utero programming of the PKC isozyme gene expression pattern in the developing heart and increases heart susceptibility to I/R injury in adult offspring.
Lawrence
Jennifer
J
Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Xiao
Daliao
D
Xue
Qin
Q
Rejali
Maryam
M
Yang
Shumei
S
Zhang
Lubo
L
D000818:Animals; D020169:Caspases / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D004198:Disease Susceptibility; D004435:Eating / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D009538:Nicotine / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051745:Protein Kinase C-delta / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
D009569:Nitric Oxide; D009538:Nicotine; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D020169:Caspases