Gestational hypertension in atrial natriuretic peptide knockout mice and the developmental origins of salt-sensitivity and cardiac hypertrophy

Armstrong, D.; Tse, M. Yat; O’Tierney-Ginn, Perrie; Wong, Philip G.; Ventura, Nicole M.; Janzen-Pang, Judy J.; Matangi, M.; Johri, Amer M.; Croy, B. Anne; Adams, Michael; Pang, Stephen C.

doi:10.1016/j.regpep.2013.08.006

Cited by 29 publications

(31 citation statements)

References 54 publications

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“…The revealed division of experimental animals into two groups according to AP changes confirms the data on salt-sensitivity reported in literature [29,30]. Sensitivity to NaCl is caused by feature of kidney function, disturbance of sympathetic nervous system, prostaglandin synthesis, RAAS activity [31][32][33]. A group of salt-sensitive animals with elevated AP was studied in this investigation.…”

Section: Biomedical Investigationssupporting

confidence: 80%

Atrial and Brain Natriuretic Peptides of Secretory Cardiomyocytes in Salt Loading in Experiment

Галкина¹,

Снопова²,

Prodanets³

et al. 2016

Sovrem Tehnol Med

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The aim of the investigation is to assess the influence of salt load on atrial (ANP) and brain (BNP) natriuretic peptide production in granules of secretory cardiomyocytes in rats.Materials and Methods. The experiments were carried out on 14 white out-bred male Wistar rats weighing 280-300 g. During the experiment all the animals were treated with standard-feed diet and had unlimited access to food and water. NaCl solution was introduced per os in the dose of 1 g per 1 kg of body mass during 14 days. Arterial pressure (AP) was measured noninvasively using a tail-cuff method. ANP and BNP production of atrial cardiomyocytes was studied by means of immunohistochemistry, transmission electron microscopy, immunocytochemistry. There was performed a morphometric analysis of granules containing peptides (A-type -"mature, storing" and B-type -"dissolving").Results. Increase in the number of granules with ANP and decrease in those with BNP accompanied by elevated AP was revealed 14 days after NaCl intake as compared to intact animals.Conclusion. Natriuretic peptides metabolism is regulated by various mechanisms. Early BNP release does not promote AP reduction due to compensatory mechanism disturbance in salt-induced arterial hypertension. Increase in ANP production occurs under the influence of renin-angiotensin-aldosterone system and elevated AP. The present data can indicate adaptive reaction in response to salt loading.

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Section: Biomedical Investigationssupporting

confidence: 80%

Atrial and Brain Natriuretic Peptides of Secretory Cardiomyocytes in Salt Loading in Experiment

Галкина¹,

Снопова²,

Prodanets³

et al. 2016

Sovrem Tehnol Med

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“…Neither heart weight nor left ventricular weight to tibia length ratios demonstrated any significant changes between groups. Blood pressure was not measured in this investigation as previous work by our laboratory has shown no differences in the blood pressure of either set of heterozygote offspring at baseline [16].…”

Section: Resultsmentioning

confidence: 95%

“…Mice were kept at room temperature (21 ± 1°C) on a 12 h light/dark cycle and fed rodent chow and tap water ad libitum. To investigate the influence of gestational hypertension on cerebral ischemia in adult offspring, heterozygous (ANP ?/-) mice were obtained through specific parental crossing and compared as previously described [16,17]. Briefly, normotensive, ANP ?/?…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we have demonstrated that chronically hypertensive female ANP gene-disrupted or knockout (ANP -/-) mice display even further significant increases in blood pressure during their pregnancy as compared to wild-type (ANP ?/? ) controls [16]. Additionally, the gestational hypertension exhibited by female ANP -/-mice does not compromise pregnancy success or offspring growth into adulthood [16].…”

Section: Introductionmentioning

confidence: 94%

“…controls [16]. Additionally, the gestational hypertension exhibited by female ANP -/-mice does not compromise pregnancy success or offspring growth into adulthood [16]. Although the absence of maternal ANP has no effect on heterozygous ANP (ANP ?/-) offspring blood pressure, we have previously demonstrated that heterozygote offspring born from ANP -/-mothers display adverse phenotypes such as increased CH, cardiac fibrosis, and diastolic dysfunction when administered isoproterenol, a moderate cardiac stressor targeting the sympathetic nervous system [17].…”

Section: Introductionmentioning

confidence: 99%

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Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring

et al. 2015

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The maternal system is challenged with many physiological changes throughout pregnancy to prepare the body to meet the metabolic needs of the fetus and for delivery. Many pregnancies, however, are faced with pathological stressors or complications that significantly impact maternal health. A shift in this paradigm is now beginning to investigate the implication of pregnancy complications on the fetus and their continued influence on offspring disease risk into adulthood. In this investigation, we sought to determine whether maternal hypertension during pregnancy alters the cerebral response of adult offspring to acute ischemic stroke. Atrial natriuretic peptide gene-disrupted (ANP(-/-)) mothers exhibit chronic hypertension that escalates during pregnancy. Through comparison of heterozygote offspring born from either normotensive (ANP(+/-WT)) or hypertensive (ANP(+/-KO)) mothers, we have demonstrated that offspring exposed to maternal hypertension exhibit larger cerebral infarct volumes following middle cerebral artery occlusion. Observation of equal baseline cardiovascular measures, cerebrovascular structure, and cerebral blood volumes between heterozygote offspring suggests no added influences on offspring that would contribute to adverse cerebral response post-stroke. Cerebral mRNA expression of endothelin and nitric oxide synthase vasoactive systems demonstrated up-regulation of Et-1 and Nos3 in ANP(+/-KO) mice and thus an enhanced acute vascular response compared to ANP(+/-WT) counterparts. Gene expression of Na(+)/K(+) ATPase channel isoforms, Atp1a1, Atp1a3, and Atp1b1, displayed no significant differences. These investigations are the first to demonstrate a fetal programming effect between maternal hypertension and adult offspring stroke outcome. Further mechanistic studies are required to complement epidemiological evidence of this phenomenon in the literature.

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Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy

et al. 2023

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ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, Setting, and ParticipantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.ExposuresThe association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.ResultsA total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).Conclusions and RelevanceThe findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.

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Gestational hypertension in atrial natriuretic peptide knockout mice and the developmental origins of salt-sensitivity and cardiac hypertrophy

Cited by 29 publications

References 54 publications

Atrial and Brain Natriuretic Peptides of Secretory Cardiomyocytes in Salt Loading in Experiment

Atrial and Brain Natriuretic Peptides of Secretory Cardiomyocytes in Salt Loading in Experiment

Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring

Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy

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