Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels.
Among the many deleterious effects of maternal smoking during pregnancy on foetal development, is a higher incidence of persistent pulmonary hypertension. The recent identification of nicotinic acetylcholine receptors (nAChR) on cells of the pulmonary vessel walls suggests that maternal smoking during pregnancy may produce morphological alterations in foetal pulmonary vasculature. Timed-pregnant rhesus monkeys were treated with nicotine (1 mg x kg(-1) x day(-1)) delivered by subcutaneous osmotic mini-pumps from days 26-134 of gestation (term: 165 days). Lung sections from 134-day foetal monkeys were used for morphometric analysis, in situ hybridisation and immunohistochemical staining. Following nicotine treatment, total wall and tunica adventitia thickness of airway associated vessels (AAV) increased significantly. Nicotine exposure significantly increased collagen I and III mRNA and protein in tunica adventitia in all AAV but not in tunica media. By contrast, levels of elastin protein were significantly decreased. alpha7 nAChR were detected in AAV fibroblasts that expressed collagen mRNA. Choline acetyltransferase, the enzyme which synthesises acetylcholine, the ligand for alpha7 nAChR was also detected in endothelium and fibroblasts. These findings suggest that with smoking during pregnancy, nicotine is transported across the placenta and directly interacts with nicotinic acetylcholine receptors in pulmonary vessels to alter connective tissue expression and therefore produce vascular structural alterations.
Sekhon
H S
HS
Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, OR 97006, USA. Sekhonh@ohsu.edu
Proskocil
B J
BJ
Clark
J A
JA
Spindel
E R
ER
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008253:Macaca mulatta; D009538:Nicotine / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D012907:Smoking
D002038:Bungarotoxins; D009538:Nicotine