Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels

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.Timed-pregnant rhesus monkeys were treated with nicotine (1 mg?kg -1 ?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. a7 nAChR were detected in AAV fibroblasts that expressed collagen mRNA. Choline acetyltransferase, the enzyme which synthesises acetylcholine, the ligand for a7 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. Eur Respir J 2004; 23: 906-915.

The Role of Nicotine in the Effects of Maternal Smoking during Pregnancy on Lung Development and Childhood Respiratory Disease. Implications for Dangers of E-Cigarettes

“…Treatment of pregnant rhesus monkeys with low levels of nicotine designed to simulate the nicotine exposure of pregnant human smokers caused marked increases of levels of a7 nAChR in airway epithelial cells and fibroblasts in fetal monkey lung ( Figures 1A and 1B). There were also increases in collagen and connective tissue in a similar distribution as the increase in a7 nAChR ( Figures 1C-1F) (56)(57)(58). Similar effects of prenatal nicotine exposure increasing lung collagen were also seen in mice (48).…”

“…The increased collagen and decreased elastin may underlie the decreased respiratory compliance observed in some studies in the offspring of mothers who smoked during pregnancy (37)(38)(39). Prenatal nicotine exposure also leads to thickening of walls surrounding airways and pulmonary vessels in monkeys (58), and this has also been reported in offspring of smokers ( Figure 1G) (59,60). In particular, the patterns of collagen expression observed in airways of offspring of smokers are strikingly similar to those observed in lungs of animals exposed just to nicotine (56)(57)(58) (Figure 1G).…”

M3 Muscarinic Receptor Antagonists Inhibit Small Cell Lung Carcinoma Growth and Mitogen-Activated Protein Kinase Phosphorylation Induced by Acetylcholine Secretion

“…Previous studies from our laboratory and other laboratories have shown that acetylcholine and M3 receptors are expressed in a wide variety of normal endothelial and epithelial cell types (5)(6)(7)(8)(9)(10)(11)(12)(13). This suggests that cancers derived from these diverse cell types will similarly coexpress acetylcholine and M3 receptors.…”

The Effect of Nicotine and its Interaction with Ethanol on Biochemical Parameters, Oxidative Damage and Histological Changes in the Rat’s Liver

“…[1][2][3][4] Moreover, it has been shown that cigarette smoking may accelerate the progression of renal, pulmonary, and cardiac fibrosis. [5][6][7] The detrimental effects of smoking have beenextensively investigated by studies of direct administration of nicotine, a major pharmacologically active component of tobacco smoke, 8 in animal and in a variety of cell systems. The predominant effects of nicotine in the whole intact animal or human consist of an increase inheart rate (10 to 20 beats/min),blood pressure (5 to 10 mmHg), release of catecholamines and free fatty acids and mobilization of blood sugar.…”