Effect of prenatal exposure to nicotine on kidney glomerular mass and AT1R expression in genetically diverse strains of rats.
Prenatal exposure to maternal cigarette smoking in humans or nicotine in experimental animals is associated with elevated blood pressure in the offspring. This effect may be limited to genetically vulnerable individuals and related to alterations in the kidneys. Here we investigated whether prenatal exposure to nicotine (PEN) alters kidney morphology and gene expression, and whether these effects differ between two genetically distant strains, i.e. spontaneously hypertensive (SHR) and Brown Norway (BN) rats. The results showed that, in SHR but not in BN offspring, PEN decreases kidney glomerular mass and increases renal expression of the angiotensin II type 1b receptor gene; the latter is not mediated through changes in DNA methylation of the proximal promoter of this gene. The results also showed that PEN alters expression of multiple genes involved in the kidney nervous system function, with mostly opposite effects being seen in SHR and BN. These results suggest that, in genetically vulnerable individuals, PEN leads to morphological and molecular changes in the kidneys that may contribute to fetal programming of hypertension.
School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom.
Maria
M
Toledo-Rodriguez
Naomi
N
Loyse
Celine
C
Bourdon
Sara
S
Arab
Zdenka
Z
Pausova
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006651:Histocytochemistry; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009538:Nicotine / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis* / Q000235:genetics
D044140:Receptor, Angiotensin, Type 1; D012313:RNA; D009538:Nicotine