Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Xiao, Daliao; Huang, Xiaohui; Lawrence, Jennifer; Yang, Shumei; Zhang, Li

doi:10.1124/jpet.106.113332

Cited by 65 publications

(88 citation statements)

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“…14 In the developing fetal lung, nicotine inhibits maturation and disrupts alveolar number, structure, and function. 15 Prenatal exposure to nicotine has also been shown to increase contractile responsiveness of the aortae to norepinephrine and KCl 16,17 and increase the susceptibility to ischemia/reperfusion injury in male rat offspring.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

et al. 2011

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This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 mg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term ¼ 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro-or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation.

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Section: Introductionmentioning

confidence: 99%

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

et al. 2011

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“…5 Our recent studies in the rat have demonstrated that fetal nicotine exposure causes reprogramming of vascular reactivity and produces genderdependent alterations in both ␣ 1 -adrenoceptor-mediated contractions and endothelial NO synthase (eNOS) activity of arteries in adult offspring. 6 In addition, fetal nicotine exposure resulted in an in utero reprogramming of protein kinase C isozyme gene expression pattern in the developing heart and increased heart susceptibility to ischemia and reperfusion injury in adult offspring. 7 Angiotensin II (Ang II) plays a fundamental role in the regulation of cardiovascular homeostasis and has been implicated in the pathophysiology of hypertension induced by adverse in utero environment during the fetal development.…”

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confidence: 99%

Prenatal Gender-Related Nicotine Exposure Increases Blood Pressure Response to Angiotensin II in Adult Offspring

Xiao

Xu²,

Huang³

et al. 2008

Hypertension

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118

156

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Abstract-Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month-old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II-stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring.In male offspring, nicotine exposure significantly increased Ang II-induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II-induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II-induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca 2ϩ concentrations and Ca 2ϩ sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor-mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring. Key Words: nicotine Ⅲ fetal programming Ⅲ gender Ⅲ angiotensin II Ⅲ vascular contractility M aternal cigarette smoking probably is the single most widespread prenatal insult in the world. Recent epidemiological studies have demonstrated that in utero exposure to maternal smoking is associated with elevated blood pressure (BP) and/or cardiovascular disease in offspring later in life. 1,2 As one of the major components in cigarette smoking, nicotine is likely to contribute to the developmental programming of cardiovascular disorders. Nicotine readily crosses the placenta, and maternal cigarette smoking produces higher nicotine concentrations in fetal circulation than that experienced by the mother. 3,4 In the developing fetus, chronic nicotine exposure resulted in permanent changes in nicotinic receptors and alterations in the activity of the central and peripheral nervous systems. 5 Our recent studies in the rat have demonstrated that fetal nicotine exposure causes reprogramming of vascular reactivity and produces genderdependent alterations in both ␣ 1 -adrenoceptor-mediated contractions and endothelial NO synthase (eNOS) activity of arteries in adult offspring. 6 In additi...

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“…Thus, fetal and neonatal nicotine exposure alters vascular functions in adult offspring in a gender-specific manner, which may lead to an increased risk of cardiovascular dysfunction in later life. 17 Furthermore, maternal smoking seems to promote stiffening of the fetal aorta during gestation. 18 Oxidant stress appears to play a major role in the inflammatory response to smoking.…”

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confidence: 99%

Smoking and Aortic Diseases

Kakafika

Mikhailidis

2007

Circ J

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Cigarette smoking is a major cause of cardiovascular disease (CVD) and is responsible for approximately 11% of the annual total CVD deaths in the United States. 1 Smoking acts synergistically with other vascular risk factors (eg, hypertension, dyslipidaemia and diabetes) to increase vascular morbidity and mortality. 2 However, smoking has a variable magnitude of increased risk for different vascular diseases: the risk is highest for peripheral arterial disease and aortic aneurysm, and is lowest for coronary artery and cerebrovascular diseases. 2 These effects are thought to reverse after smoking cessation. The constituents of cigarette smoke with the major contribution to pathogenesis of vascular disease are nicotine, carbon monoxide, oxidant gases and polycyclic aromatic hydrocarbons. 2 Nonsmokers who are exposed to "secondhand" smoke experience on average a 30% excess risk of ischemic heart disease and nonfatal myocardial infarction. 3 Secondhand smoke exposure has been shown to activate platelets and to produce endothelial dysfunction, in both experimental animals and humans. 3 The mechanisms by which smoking causes acute cardiovascular events include endothelial dysfunction, thrombosis and inflammation.Endothelial dysfunction is an initiating event in atherogenesis, as well as a major factor in causing acute cardiovascular events. Cigarette smoking impairs flow-mediated endothelium-dependent peripheral arterial vasodilatation, an effect that is, at least partly, reversible after smoking Circulation Journal Vol.71, August 2007 cessation. 4 Smokers without atherosclerosis have coronary vasoconstrictor responses to acetylcholine that, in the presence of normal endothelium, produce vasodilatation. 5 Indeed, the oxidant chemicals of smoke degrade nitric oxide (NO) and reduce NO release, with subsequent impairment of vascular dilation and platelet function. 2 Smokers have lower than normal levels of antioxidant vitamins, reflecting their consumption in response to ongoing oxidant stress. 6 In addition, nicotine itself alters the structural and functional characteristics of vascular smooth muscle cells (VSMC) and endothelial cells. 7,8 Experimental data show that human aortic endothelial cells undergo apoptotic changes when they are exposed to cigarette smoke extracts. 9 This process may be prevented by pre-activation of NO synthase by Larginine. 9,10 Furthermore, smoking causes an increase in vascular superoxide production, which results in decreased NO bioactivity and concomitantly increases production of vasoconstrictor eicosanoids. 11 Cigarette smoke extracts, but not nicotine, also inhibit prostacyclin (PGI2: a vasodilator and inhibitor of platelet aggregation) synthesis in human, rabbit and rat vascular tissue. 12 Smoking-mediated endothelial dysfunction also results in reduced secretion of tissue plasminogen activator (tPA) 13 and increased secretion of plasminogen activator inhibitor (PAI)-1, 1 which results in impaired fibrinolysis. This acts in concert with the increased levels of tissue factor and fibrin...

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Fetal and Neonatal Nicotine Exposure Differentially Regulates Vascular Contractility in Adult Male and Female Offspring

Cited by 65 publications

References 42 publications

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

Prenatal Gender-Related Nicotine Exposure Increases Blood Pressure Response to Angiotensin II in Adult Offspring

Smoking and Aortic Diseases

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