Developmental Programming of Hypertension

Dasinger, John Henry; Davis, Gwendolyn K.; Newsome, Ashley D.; Alexander, Barbara T.

doi:10.1161/hypertensionaha.116.06603

Cited by 45 publications

(42 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alterations of the RAAS and proinflammatory cytokines in peripheral tissues and plasma have been implicated as important mediators in the fetal programming of increased BP. 30 Washburn et al found increased plasma aldosterone levels in male adolescents born to mothers with preeclampsia. 8 In animal experiments, the offspring from dams with protein restriction, 11,12 diabetes 19 or inflammation 20 showed significant increases in intrarenal RAAS components such as angiotensinogen and ANG II, renal and arterial proinflammatory cytokines and pulmonary and plasma ACE activity, which were associated with higher BP in these offspring.…”

Section: Discussionmentioning

confidence: 98%

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

et al. 2017

View full text Add to dashboard Cite

P reeclampsia and gestational hypertension are common conditions affecting 5% to 7% of all pregnancies.1 Multiple casecontrol and cohort studies have demonstrated that offspring of hypertensive pregnancies have higher blood pressure (BP) in childhood and adolescence and are at increased risk of developing adult hypertension. [2][3][4][5][6][7] Studies investigating the mechanisms that contribute to the development of hypertension in the offspring of mothers with preeclampsia and gestational hypertension found that male adolescents had increased aldosterone levels, a trend for increased circulating renin activity 8 and increased sympathetic activity before and during isometric exercise. 9 These results suggest the renin-angiotensin-aldosterone system (RAAS) and sympathetic nerve activity (SNA) are involved in the development of higher BP in the offspring of mothers with high BP during pregnancy.Animal experiments have shown that uteroplacental insufficiency, protein restriction, chronic secondary hypertension, or glucocorticoid treatment during pregnancy leads to hypertension in the offspring. 10 Consistent with the RAAS and SNA playing a role in mediating the fetal programming of hypertension, several studies have demonstrated that both captopril, an angiotensin-converting enzyme-1 (ACE1) inhibitor, and losartan, an angiotensin II (ANG II) receptor blocker, administered in the drinking water reduced increased BP in the offspring of dams fed low-protein diet 11,12 and of spontaneously hypertensive rats, 13 whereas renal denervation (RD) abolished hypertension in the offspring from diabetic rats 14 or from pregnant rats with reduced uterine perfusion. 15,16 Moreover, Mizuno et al 17,18 demonstrated that the RAAS contributes to the enhancement of the renalAbstract-Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensinconverting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in mal...

show abstract

Section: Discussionmentioning

confidence: 98%

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A central mediator of RAS control on blood pressure is angiotensin-converting enzyme (ACE). ACE cleaves angiotensin I to form angiotensin II, a potent regulator of vascular function and blood volume (Dasinger et al 2016). In rodents, offspring of dams fed diets high in fat (Zhang et al 2018) and salt (Mao et al 2013) or low in protein (Watkins et al 2010) have all been shown to program offspring cardiovascular dysfunction via impaired RAS regulation.…”

Section: Introductionmentioning

confidence: 99%

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

Key points A low protein diet had minimal effects on paternal cardiovascular function or renin–angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin–angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1 male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin‐converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner. Abstract Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup‐optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin‐converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin–angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub‐optimal paternal nutrition on offspring cardiovascular well‐being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.

show abstract

“…In this context, gestational protein restriction is followed by low birthweight in rats which in turn, leads to gender-related changes in blood pressure, kidney function, glucose metabolism, and anxiety-like behaviors in male compared to female offspring. The sex hormones contribute to a sexual phenotype dimorphism in the fetal programming model of adult disease by modulating regulatory pathways critical in the long-term control of neural, cardiovascular, and metabolic functions [1][2][3][4][5][6][7][8][35][36][37][38][39]. Thus, this study was conducted only in male rats to ward-off interference from gender differences.…”

Section: Discussionmentioning

confidence: 99%

“…Environmental and genetic factors influence the ontogenetic development, and on adverse circumstance, eventually leading to functional and structural disorders of tissues and organs. In rats, gestational protein restriction is associated with low birthweight, fewer nephrons, and increased risk for the development of heart diseases, kidney dysfunction and metabolic syndrome in adult life [1][2][3][4][5][6][7]. We recently demonstrated that maternal low-protein (LP) intake offspring have a lower birth weight, 30% fewer nephrons, and arterial hypertension [3,4,6] when compared with age-matched, normal (NP) protein intake group.…”

Section: Introductionmentioning

confidence: 99%

“…We recently demonstrated that maternal low-protein (LP) intake offspring have a lower birth weight, 30% fewer nephrons, and arterial hypertension [3,4,6] when compared with age-matched, normal (NP) protein intake group. Additionally, water and salt balance studies have shown that hypertension in LP offspring is associated with decreased urinary sodium excretion [3][4][5][6][7][8]. The involvement of the central nervous system (CNS) in the control of blood pressure and, water and salt homeostasis has been demonstrated in several studies [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of intracerebroventricular epinephrine microinjection on blood pressure and urinary sodium handling in gestational protein-restricted rat adult male offspring

Gontijo

Bôer

Custódio

et al. 2018

Preprint

View full text Add to dashboard Cite

Background. In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (i.c.v.) microinjected adrenergic agonists are involved in the development of hypertension in maternal low-protein (LP) intake offspring. Methods. Stainless steel cannula was stereotaxically implanted into the right lateral ventricle, by use of techniques reported elsewhere and after that, was evaluated the effect of i.c.v. injection of adrenergic agonists, at increasing concentrations, and of α1 and α2-adrenoceptor antagonists on blood pressure and urinary sodium handling in LP offspring relative to age-matched, normal (NP) protein intake group. Results. We confirmed that epinephrine (Epi) microinjected into the lateral ventricle (LV) of conscious NP rats leads to enhanced natriuresis followed by a reduction in arterial pressure. This response was associated with increased proximal and post-proximal sodium excretion accompanied by an unchanged glomerular filtration rate. The current study showed in both, NP and LP offspring that natriuretic effect of Epi injection into the LV was abolished by prior local microinjection of an α1adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of epinephrine. The LV yohimbine pretreatment normalized urinary sodium excretion and reduced the blood pressure in LP compared with age-matched NP offspring. Conclusion. These are, as far as we are aware, the first results showing the role of central adrenergic receptors interaction on hypertension pathogenesis in maternal protein-restricted fetal programming offspring. The study also provides good evidence of the existence of central nervous system adrenergic mechanisms consisting of α1 and α2-adrenoceptors, which works reciprocally on the control of renal sodium excretion and blood pressure. Although the precise mechanism of the different natriuretic response of NP and LP rats is still uncertain, these results led us to speculate that inappropriate neural adrenergic pathways might have significant effects on tubule sodium transport, resulting in the inability of the kidneys to control hydrosaline balance, and, consequently, an increase in blood pressure.3

show abstract

Developmental Programming of Hypertension

Cited by 45 publications

References 51 publications

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Effect of intracerebroventricular epinephrine microinjection on blood pressure and urinary sodium handling in gestational protein-restricted rat adult male offspring

Contact Info

Product

Resources

About