Fetal and neonatal nicotine exposure differentially regulates vascular contractility in adult male and female offspring.
Epidemiologic studies suggest that prenatal exposure to maternal cigarette smoking is associated with an increased risk of elevated blood pressure in postnatal life. The present study was designed to test the hypothesis that fetal and neonatal nicotine exposure increased vascular contractility in adult offspring. Nicotine was administered to pregnant rats via s.c. osmotic minipumps throughout gestation and up to 10 days after delivery. Aortas were isolated from adult male and female offspring at the age of 3 months old. Nicotine significantly increased KCl- and norepinephrine-induced contractions of the aorta in male, but not female, offspring. Inhibition of endothelial nitric oxide synthase (eNOS) with N(G)-nitro-L-arginine (L-NNA) significantly increased norepinephrine-induced contractions in control male offspring but showed no effect in nicotine-treated male offspring. In the presence of L-NNA, there was no significant difference in norepinephrine-induced contractions between control and nicotine-treated males. In contrast, nicotine caused a significant increase in L-NNA-mediated potentiation of norepinephrine-induced contractions in female offspring. Nicotine had no effect on sodium nitroprusside-induced endothelium-independent relaxations of aortas from either male or female offspring. However, it decreased endothelium-dependent relaxations induced by acetylcholine in male offspring but increased them in females. There were no differences in eNOS protein levels in aortas between the control and nicotine-treated animals in either male or female offspring. The results suggest that fetal and neonatal nicotine exposure alters vascular functions in adult offspring in a gender-specific manner, which may lead to an increased risk of cardiovascular dysfunction in later life.
Xiao
DaLiao
D
Center for Perinatal Biology, Department of Pharmacology and Physiology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dxiao@llu.edu
Huang
Xiaohui
X
Lawrence
Jennifer
J
Yang
Shumei
S
Zhang
Lubo
L
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008098:Litter Size / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D019335:Nitroarginine; D011189:Potassium Chloride; D009538:Nicotine; D052250:Nitric Oxide Synthase Type III; D002118:Calcium; D009638:Norepinephrine