Long-term effect of a chronic low-protein multideficient diet on the heart: Hypertension and heart failure in chronically malnourished young adult rats

Mendes, Luiza V.P.; Gonsalez, Sabrina R.; Oliveira-Pinto, Leonardo Maciel; Pereira‐Acácio, Amaury; Takiya, Christina Maeda; Nascimento, José; Einicker‐Lamas, Marcelo; Vieyra, Adalberto; Cunha, Valéria M.N.; Lara, Lucienne S.

doi:10.1016/j.ijcard.2017.03.110

Cited by 9 publications

(10 citation statements)

References 49 publications

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“…2 clearly shows the strongly negative influence of the poor quality of the RBD on the development of rats. Reduced body mass is accompanied by reduced kidney and heart mass, and Supplementary Table 2 indicates that malnutrition affected the 2 organs in an opposite manner: whereas the renal index remained unmodified, the significant relative increase in heart mass with respect to body mass points to ongoing processes of cardiac hypertrophy and heart failure that are key elements of structural remodeling [50,51] associated to electrical remodeling [8,52]. The chronic administration of Los (alone or in are differences in putative phosphorylatable sites [9], which probably control catalysis in physiological and pathological conditions and confer some functional dissimilarity to each other.…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats

Muzi‐Filho

Bouzan

Alves-Barros

et al. 2020

Cell Physiol Biochem

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BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

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Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats

Muzi‐Filho

Bouzan

Alves-Barros

et al. 2020

Cell Physiol Biochem

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“…Cardiac Ca 2+ handling is regulated by Ang II in physiological and pathological conditions, and PMCA and SERCA are responsible for the primary active Ca 2+ transport across the respective membranes. Moreover, we have shown already that upregulation of PMCA and downregulation of SERCA–considered biomarkers of cardiac lesionswere accompanied by histological evidence of ventricular atrophy and recent infarct lesions. Saline programming increased cardiac PMCA, which was differently modulated by α‐Tocopherol (Figure ).…”

Section: Discussionmentioning

confidence: 79%

Alpha‐Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Cabral

Vieira‐Filho

Sant'Helena

et al. 2019

Clin Exp Pharma Physio

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Maternal salt overload programs cardiovascular and renal alterations in the offspring.However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 mol/L NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr Cl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to

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“…In contrast, impaired cardiomyocyte contractility, lower calcium amplitude, reduced cardiomyocyte size, and increased number of collagen fibers in the LV myocardium in response to a postweaning LP diet was reported (Penitente et al, 2013(Penitente et al, , 2014. Such differences may be related to the stage of the hypertensive disease induced by postweaning protein restriction (Mendes et al, 2017) as well as to differences in LP diet composition. A limitation of our study is that the hemodynamic LV measurements were performed in anesthetized animals.…”

Section: Discussionmentioning

confidence: 96%

Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A

García‐Arévalo

Lorza‐Gil

Cardoso³

et al. 2021

Front. Physiol.

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Bisphenol-A (BPA) is an endocrine disruptor associated with higher risk of insulin resistance, type 2 diabetes, and cardiovascular diseases especially in susceptible populations. Because malnutrition is a nutritional disorder associated with high cardiovascular risk, we sought to compare the effects of short-term BPA exposure on cardiovascular parameters of healthy and protein-malnourished mice. Postweaned male mice were fed a normo- (control) or low-protein (LP) diet for 8 weeks and then exposed or not to BPA (50 μg kg−1 day−1) for the last 9 days. Systolic blood pressure was higher in BPA or LP groups compared with the control group. However, diastolic blood pressure was enhanced by BPA only in malnourished mice. Left ventricle (LV) end diastolic pressure (EDP), collagen deposition, and CTGF mRNA expression were higher in the control or malnourished mice exposed to BPA than in the respective nonexposed groups. Nevertheless, mice fed LP diet exposed to BPA exhibited higher angiotensinogen and cardiac TGF-β1 mRNA expression than mice treated with LP or BPA alone. Wall:lumen ratio and cross-sectional area of intramyocardial arteries were higher either in the LP or BPA group compared with the control mice. Taken together, our data suggest that short-term BPA exposure results in LV diastolic dysfunction and fibrosis, and intramyocardial arteries inward remodeling, besides potentiate protein malnutrition-induced hypertension and cardiovascular risk.

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Long-term effect of a chronic low-protein multideficient diet on the heart: Hypertension and heart failure in chronically malnourished young adult rats

Cited by 9 publications

References 49 publications

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats

Alpha‐Tocopherol during lactation and after weaning alters the programming effect of prenatal high salt intake on cardiac and renal functions of adult male offspring

Ventricular Fibrosis and Coronary Remodeling Following Short-Term Exposure of Healthy and Malnourished Mice to Bisphenol A

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