Prenatal exposure to nicotine modifies kidney weight and blood pressure in genetically susceptible rats: a case of gene-environment interaction.
BACKGROUND
Epidemiologic studies suggest that in utero exposure to maternal smoking is associated with elevated blood pressure (BP) later in life. Our aims were: (1) to examine effects of intrauterine exposure to nicotine on BP and hypertension target-organ size in rats; and (2) to investigate whether such effects depend on genetic background, by studying two genetically distinct strains of rats: the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN) rat.


METHODS
Nicotine or saline was administered to dams via subcutaneous osmotic minipumps throughout gestation. In nine-week-old male offspring, we measured BP and heart rate, assessed the weight of kidneys and heart, and determined fasting levels of glucose, insulin, triglycerides (TG), and cholesterol. We also measured gene expression of the insulin-like growth factor (IGF) system in the liver and kidneys.


RESULTS
SHR and BN offspring differed in their response to intrauterine exposure to nicotine. SHR exposed to nicotine (vs. saline) exhibited higher BP (P < 0.02) and serum cholesterol levels (P = 0.01), and lower kidney weight (P < 0.0001). In contrast, BN rats did not demonstrate differences between the nicotine and saline groups in these variables, but the nicotine-exposed BN rats showed a significant up-regulation in the gene expression of IGF-1 in the liver (P < 0.0001) and IGF receptor in the kidney (P = 0.006).


CONCLUSIONS
These results suggest that intrauterine exposure to nicotine alters the cardiovascular system depending on the genetic background and, as such, supports the notion that the intrauterine environment interacts with genes in determining an individual's health later in life.
Pausová
Zdenka
Z
Centre de recherche, Centre hospitalier de l'Université de Montréal, Montréal, Canada. zdenka.pausova@umontreal.ca
Paus
Tomás
T
Sedová
Lucie
L
Bérubé
Julie
J
D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000254:growth & development; D002784:Cholesterol / Q000097:blood; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology* / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics; D011918:Rats, Inbred SHR / Q000235:genetics; D017451:Receptors, Somatomedin / Q000378:metabolism; D015854:Up-Regulation
D018722:Nicotinic Agonists; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D009538:Nicotine; D002784:Cholesterol; D005947:Glucose