Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy

Leiva, Andrea; Fuenzalida, Bárbara; Barros, Eric; Sobrevia, Bastián; Salsoso, Rocío; Sáez, Tamara; Villalobos, Rodrigo; Silva, L.; Chiarello, Indira; Toledo, Fernando; Gutiérrez, Jaime; Sanhueza, Carlos; Pardo, Fabián; Sobrevía, Luis

doi:10.2174/1570161114666160222115158

Cited by 42 publications

(28 citation statements)

References 289 publications

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“…In addition, pregnant women have a three times greater risk of dying from flu and malaria than nonpregnant (NP) women [2], suggesting that pregnant women are particularly vulnerable to some types of infection. This may be related to various pregnancy-induced adaptations: (i) suppression of the acquired immune system [3]; (ii) excessive activation of the innate immune system, which is thought to be responsible for preterm labor (PTL) [4] and some cases of cerebral palsy [5]; and (iii) higher levels of nitric oxide may exacerbate sepsis-induced hypotension and enhance the excessive innate immune response [6,7]. Although septic shock is a major cause of mortality in intensive care units worldwide, remarkably little is known about the impact of sepsis on cardiovascular function during pregnancy [8], especially the adaptation and regulation of the peripheral vascular system.…”

Section: Introductionmentioning

confidence: 99%

The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice†

Zöllner

Howe

Edey

et al. 2017

Biology of Reproduction

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Sepsis is the leading cause of direct maternal mortality, but there are no data directly comparing the response to sepsis in pregnant and nonpregnant (NP) individuals. This study uses a mouse model of sepsis to test the hypothesis that the cardiovascular response to sepsis is more marked during pregnancy. Female CD1 mice had radiotelemetry probes implanted and were time mated. NP and day 16 pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 μg, serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and flow cytometry studies), aorta and uterine vessels (for wire myography) were collected after LPS or vehicle control administration. Administration of LPS resulted in a greater fall in blood pressure in pregnant mice compared to NP mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors, and circulating leukocytes, but with a greater monocyte and lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of cardiac dysfunction and apoptosis as well as cytokine expression were higher in pregnant mice, but the response to LPS was similar in both groups as was the ex vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response. We conclude that endotoxemia induces a more marked hypotensive response in pregnant compared to NP mice. These changes were not associated with a more marked systemic inflammatory response in pregnant mice, although monocyte lung margination was greater. The more marked hypotensive response to LPS may explain the greater vulnerability to some infections exhibited by pregnant women. Pregnancy enhances LPS-induced hypotension, 2017, Vol. 97, No. 2 Summary SentenceIn pregnant mice, nonfatal sepsis is associated with a more marked hypotensive response but not a greater immune response.

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Section: Introductionmentioning

confidence: 99%

The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice†

Zöllner

Howe

Edey

et al. 2017

Biology of Reproduction

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“…Several previous studies reported that moderate iron intake in non‐anemic pregnant women could induce glycemic disorder, hyperinsulinemia and oxidative damage in their offspring, and that fetal hyperinsulinemia was positively correlated with macrosomia. Interestingly, both pregnant women and their newborns showed euglycemia after treatment with diet; however, metabolic alternation of OS in the fetoplacental vasculature was seen, including endothelial dysfunction, which was likely associated with hyperinsulinemia of the fetus and thereby leading to macrosomia. Although their PG was normal, non‐GDM pregnant women with a high concentration of plasma ferritin might induce fetal hyperinsulinemia and oxidative damage in their offspring, leading to metabolic alternation by OS; thereby, it was likely associated with macrosomia.…”

Section: Discussionmentioning

confidence: 95%

Correlation between plasma ferritin level and gestational diabetes mellitus and its impact on fetal macrosomia

Wang

Fan

Yang

et al. 2018

J of Diabetes Invest

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Aims/IntroductionTo explore the relationship between plasma iron levels and gestational diabetes mellitus, as well as its impact on macrosomia.Materials and MethodsWe retrospectively compared ferritin level and other characteristics between pregnant women with gestational diabetes mellitus (GDM) and pregnant women without GDM. The correlation between the levels of plasma ferritin, glucose and hemoglobin was explored. Meanwhile, we assessed the risk factors of macrosomia. Furthermore, we explored the relationship between ferritin level and the incidence of macrosomia.ResultsA total of 793 pregnant women were enrolled in the present study, of which 92 pregnant women had GDM and 701 pregnant women were healthy. Meanwhile, 51 pregnant women gave birth to infants with macrosomia and another 742 women had normal infants. Compared with non‐GDM women, pregnant women with GDM were older, with higher pre‐pregnancy body mass index, plasma ferritin, fasting plasma glucose, 1‐h postprandial glucose, 2‐h plasma glucose and hemoglobin. In addition, our results showed a significant positive correlation between the levels of ferritin and fasting plasma glucose when ferritin levels were >70 ng/mL. Our results also showed that pre‐pregnancy overweight or obesity, a high concentration of ferritin, as well as abnormal levels of fasting plasma glucose, 1‐h plasma glucose and 2 h plasma glucose were risk factors for macrosomia. Furthermore, as the level of ferritin increased, so did the incidence of macrosomia.ConclusionsThe current study provides evidence that pregnant women with high levels of ferritin might be prone to GDM. In addition, a high level of ferritin might be an independent risk factor for macrosomia. Therefore, the negative effect of iron supplementation in non‐anemic pregnant women might be noteworthy.

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“…16 These findings add to previously reported work suggesting a link between maternal and fetal nitrogen oxide metabolism and disease. 17, 18 …”

Section: Discussionmentioning

confidence: 99%

Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung

et al. 2017

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Background/Objectives:Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice.Methods:We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring.Results:Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring.Conclusions:These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

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Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy

Cited by 42 publications

References 289 publications

The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice†

The response of the innate immune and cardiovascular systems to LPS in pregnant and nonpregnant mice†

Correlation between plasma ferritin level and gestational diabetes mellitus and its impact on fetal macrosomia

Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung

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