Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels
Open Access
- 1 June 2004
- journal article
- Published by European Respiratory Society (ERS) in European Respiratory Journal
- Vol. 23 (6), 906-915
- https://doi.org/10.1183/09031936.04.00069604
Abstract
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. Timedpregnant rhesus monkeys were treated with nicotine (1 mg·kg−1·day−1) delivered by subcutaneous osmotic minipumps 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. α7 nAChR were detected in AAV fibroblasts that expressed collagen mRNA. Choline acetyltransferase, the enzyme which synthesises acetylcholine, the ligand for α7 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.Keywords
This publication has 16 references indexed in Scilit:
- Normal Patterns of Angiogenesis and Extracellular Matrix Deposition in Chick Chorioallantoic Membranes Are Disrupted by Mainstream and Sidestream Cigarette SmokeToxicology and Applied Pharmacology, 2000
- Nicotine Regulates Basic Fibroblastic Growth Factor and Transforming Growth Factor β1Production in Endothelial CellsBiochemical and Biophysical Research Communications, 1999
- Prenatal nicotine increases pulmonary α7 nicotinic receptor expression and alters fetal lung development in monkeysJCI Insight, 1999
- THE CHOLINERGIC ‘PITFALL’: ACETYLCHOLINE, A UNIVERSAL CELL MOLECULE IN BIOLOGICAL SYSTEMS, INCLUDING HUMANSClinical and Experimental Pharmacology and Physiology, 1999
- Nicotine and cotinine stimulate secretion of basic fibroblast growth factor and affect expression of matrix metalloproteinases in cultured human smooth muscle cellsJournal of Vascular Surgery, 1996
- The Effect of Cigarette Smoking on Neonatal Anthropometric MeasurementsObstetrics & Gynecology, 1995
- Synthesis and release of acetylcholine by cultured bovine arterial endothelial cellsNeuroscience Letters, 1990
- Fetal Lung Hypoplasia Associated with Maternal Smoking: A Morphometric AnalysisPediatric Research, 1985
- Distribution of pulmonary cholinergic nerves in the rabbit.Thorax, 1982
- Cigarette Smoking Induces Functional Antiprotease Deficiency in the Lower Respiratory Tract of HumansScience, 1979