Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia

Mimura, Kazuya; Tomimatsu, Takuji; Sharentuya, Namuxila; Tskitishvili, Ekaterine; Kinugasa-Taniguchi, Yukiko; Kanagawa, Takeshi; Kimura, Tadashi

doi:10.1016/j.ajog.2010.01.037

Cited by 37 publications

(29 citation statements)

References 52 publications

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“…The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the PI3K/AKT pathway and are caused by the release of endothelium-derived NO. These findings provide further evidence showing that nicotinic receptors can modulate physiological and pathophysiological processes in non-neuronal tissues and organ systems (Wang et al, 2004;Egleton et al, 2008;Mimura et al, 2010). In addition to their involvements in angiogenesis, oxidative and phagocytic activity of macrophages, and the proinflammatory and proapoptotic actions of cytokines on endothelial cells (Lee and Cooke, 2011), nicotinic receptors …”

Section: Discussionmentioning

confidence: 52%

Activation of Nicotinic Receptors Can Contribute to Endothelium-Dependent Relaxations to Acetylcholine in the Rat Aorta

Zhang

Leung²,

Vanhoutte³

2012

J Pharmacol Exp Ther

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Acetylcholine causes endothelium-dependent relaxations in the rat aorta. Both muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs) are expressed in endothelial cells. It is generally accepted that mAChRs are responsible for the endothelium-dependent relaxations evoked by acetylcholine. The present study was designed to investigate whether nAChRs can also be involved in such responses evoked by the cholinergic transmitter. Rings with or without endothelium of aortae of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were suspended in organ chambers for the measurement of isometric tension. In WKY aortae the muscarinic antagonist atropine abolished the relaxations to increasing concentrations of acetylcholine, confirming that mAChRs are responsible mainly for the response under control conditions. In SHR aortae, atropine caused only partial inhibition of the endothelium-dependent relaxations to acetylcholine; the remaining decreases in tension were inhibited by the nicotinic antagonist mecamylamine, which did not significantly affect the response in the absence of atropine in either SHR or WKY preparations. Thus, when mAChRs are inhibited, nAChRs mediate relaxation to the cholinergic transmitter in the SHR but not the WKY aorta. Nicotine, a direct agonist of the nicotinic receptor, induced endothelium-dependent relaxations in both SHR and WKY rats via the activation of ␣7-nAChRs, but not by mecamylamine-sensitive nicotinic receptors (␣3 subtype). The acetylcholine-induced, atropine-insensitive relaxations and those to nicotine both involve the phosphatidylinositol 3-kinase/AKT pathway. The present study demonstrates that the activation of nAChRs can contribute to acetylcholine-induced, endothelium-dependent relaxations in the aortae of hypertensive animals and suggests that these receptors may contribute to the endothelium-dependent regulation of vascular tone.

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Section: Discussionmentioning

confidence: 52%

Activation of Nicotinic Receptors Can Contribute to Endothelium-Dependent Relaxations to Acetylcholine in the Rat Aorta

Zhang

Leung²,

Vanhoutte³

2012

J Pharmacol Exp Ther

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“…Smoking may protect from developing preeclampsia by different mechanisms, mainly through modulating the expression of angiogenic factors [40,41]. Here, we report that high placental expression of VEGFA in smoking women was evident at 10-11 weeks of gestation.…”

Section: Discussionmentioning

confidence: 77%

Maternal Smoking and Placental Expression of a Panel of Genes Related to Angiogenesis and Oxidative Stress in Early Pregnancy

et al. 2014

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Objective: Maternal cigarette smoking is paradoxically associated with a decreased risk of developing preeclampsia. Since preeclampsia is thought to be associated with altered mechanisms of angiogenesis and oxidative stress, we aim to investigate the influence of maternal smoking on the early placental expression of a panel of genes related to angiogenesis and oxidative stress. Material and Methods: We collected villous tissue samples at 6-7 and 10-11 weeks of gestation from 31 women requesting surgical termination. Placental expression of the following genes were quantified by real-time PCR: vascular endothelial growth factor A (VEGFA), fms-like tyrosine kinase (Flt-1), soluble endoglin (sEng), placental growth factor (PlGF), heme oxygenase-1 (HMOX-1) and superoxide dismutase (SOD). Maternal smoking status was assessed by levels of serum cotinine. Results: Placental expression of VEGFA was significantly higher in smoking women at 10-11 weeks of gestation compared with nonsmoking women at the same gestational age. There was no significant difference at 6-7 weeks of gestation. There was no variation in the expression of the other genes explored related to smoking status. Conclusions: Here we report that VEGFA placental expression was higher in smoking women at 10-11 weeks of gestation. Increased VEGFA expression in the early stages of pregnancy in smoking women might contribute to the decreased risk of developing preeclampsia.

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“…Even the apparent protective effect of smoking is being investigated in a 'desperate' therapeutic search against preeclampsia [66]. To date, early (first-trimester) prediction of preeclampsia remains elusive, although recent combined screening models show promise [67].…”

Section: Discussionmentioning

confidence: 99%

New therapeutic approaches to treating hypertension in pregnancy

Mate¹,

Vázquez²,

Leiva³

et al. 2012

Drug Discovery Today

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Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia

Cited by 37 publications

References 52 publications

Activation of Nicotinic Receptors Can Contribute to Endothelium-Dependent Relaxations to Acetylcholine in the Rat Aorta

Activation of Nicotinic Receptors Can Contribute to Endothelium-Dependent Relaxations to Acetylcholine in the Rat Aorta

Maternal Smoking and Placental Expression of a Panel of Genes Related to Angiogenesis and Oxidative Stress in Early Pregnancy

New therapeutic approaches to treating hypertension in pregnancy

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