Maternal protein restriction compromises myocardial contractility in the young adult rat by changing proteins involved in calcium handling

2016 ◽  
Vol 120 (3) ◽  
pp. 344-350 ◽  
Author(s):  
Aucelia C. S. de Belchior ◽  
David D. Freire ◽  
Carlos P. da Costa ◽  
Dalton V. Vassallo ◽  
Alessandra S. Padilha ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Young Adult ◽  
Left Ventricular ◽  
Protein Restriction ◽  
Female Rats ◽  
Male Rats ◽  
Calcium Handling ◽  
Myocardial Mechanics ◽  
Maternal Protein Restriction ◽  
Calcium Handling Proteins

Maternal protein restriction (MPR) during pregnancy is associated with increased cardiovascular risk in the offspring in adulthood. In this study we evaluated the cardiac function of young male rats born from mothers subjected to MPR during pregnancy, focusing on the myocardial mechanics and calcium-handling proteins. After weaning, rats received normal diet until 3 mo old, when the following parameters were assessed: arterial and left ventricular hemodynamics and in vitro cardiac contractility in isolated papillary muscles. The body weight was lower and arterial pressure higher in the MPR group compared with young adult offspring of female rats that received standard diet (controls); and left ventricle time derivatives increased in the MPR group. The force developed by the cardiac muscle was similar; but time to peak and relaxation time were longer, and the derivatives of force were depressed in the MPR. In addition, MPR group exhibited decreased post-pause potentiation of force, suggesting reduced reuptake function of the sarcoplasmic reticulum. Corroborating, the myocardial content of SERCA-2a and phosphorylated PLB-Ser16/total PLB ratio was decreased and sodium-calcium exchanger was increased in the MPR group. The contraction dependent on transsarcolemmal influx of calcium was higher in MPR if compared with the control group. In summary, young rats born from mothers subjected to protein restriction during pregnancy exhibit changes in the myocardial mechanics with altered expression of calcium-handling proteins, reinforcing the hypothesis that maternal malnutrition is related to increased cardiovascular risk in the offspring, not only for hypertension, but also cardiac dysfunction.

Modest maternal protein restriction fails to program adult hypertension in female rats

2005 ◽  
Vol 289 (4) ◽  
pp. R1131-R1136 ◽  
Author(s):  
Lori L. Woods ◽  
Julie R. Ingelfinger ◽  
Ruth Rasch
Keyword(s):  
Renin Angiotensin System ◽  
Female Gender ◽  
Female Offspring ◽  
Protein Restriction ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Angiotensin System ◽  
Low Protein ◽  
Maternal Protein Restriction

Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50–65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 ± 3 mmHg vs. NP: 121 ± 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 ± 2,071 vs. NP: 26,248 ± 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 ± 0.11 106μm3, LP vs. NP: 1.07 ± 0.11 106μm3); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender.

P943The effects of ovariectomy on guinea pig cardiomyocyte intracellular calcium regulation and phosphorylation

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Ching ◽  
J M Firth ◽  
A J Francis ◽  
N Islam ◽  
K T Macleod
Keyword(s):  
Intracellular Calcium ◽  
Calcium Regulation ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Time To Peak ◽  
Oestrogen Deficiency ◽  
Calcium Handling Proteins ◽  
Presence And Absence ◽  
Intracellular Calcium Regulation

Abstract Background Differences in cardiovascular disease risk between men and women have been partly attributed to the cardioprotective effects of oestrogen. Long-term oestrogen deficiency has been shown to alter cardiomyocyte intracellular calcium handling, but little is known about the mechanisms by which these changes occur. Oestrogen is thought to induce both genomic and non-genomic effects on cardiomyocytes, the latter including phosphorylation of calcium handling proteins. Purpose This study addresses the hypothesis that long-term oestrogen deficiency increases protein kinase A (PKA) and calcium/calmodulin-dependent kinase II (CaMKII) phosphorylation in cardiomyocytes, resulting in altered intracellular calcium regulation. Methods Female guinea pigs underwent sham (n = 7) or ovariectomy (OVx) (n = 8) operations and 150 days later, left ventricular myocytes were enzymatically isolated and loaded with fluo-4AM to monitor intracellular calcium. Calcium transients (CaT) were recorded using confocal microscopy. PKA and CaMKII phosphorylation were inhibited by superfusing cells with specific inhibitors, PKI and AIP, respectively. Experiments were carried out both in the presence and absence of β-agonist, isoprenaline (ISO), and relative changes to CaT parameters compared between OVx and sham cells. Results CaT amplitude was greater (p < 0.05) in the OVx group (ΔF/Fo= 2.51 ± 0.57) compared with sham (ΔF/Fo = 2.16 ± 0.57). Inhibition of CaMKII phosphorylation increased CaT amplitude in the sham but not OVx group, both in the presence (by 22%, p < 0.01) and absence of ISO (by 19%, p < 0.01). Time to peak of the CaT increased to a greater extent following inhibition of PKA and CaMKII phosphorylation in the OVx group compared with sham, both in the presence (by 69%, p < 0.0001) and absence (by 162%, p < 0.0001) of ISO respectively. CaT decay time significantly increased (by 21%, p < 0.01) in the sham group following inhibition of PKA and CaMKII together, whilst decay times in the OVx group remained unchanged in the presence and absence of ISO. At higher pacing rates, time to peak of the CaT decreased significantly (by 48%, p < 0.01) in the OVx group but not sham with inhibition of phosphorylation. Conclusion Our findings suggest ovariectomy alters intracellular calcium regulation and some of these effects appear to be mediated by alterations in phosphorylation of calcium handling proteins and/or changes to sites of phosphorylation.

scholarly journals Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring

2019 ◽  
Vol 20 (3) ◽  
pp. 469 ◽  
Author(s):  
Marilia Martins Cavariani ◽  
Talita de Mello Santos ◽  
Dhrielly Natalia Pereira ◽  
Luiz Gustavo de Almeida Chuffa ◽  
Patricia Fernanda Felipe Pinheiro ◽  
...  
Keyword(s):  
Protein Restriction ◽  
Male Rats ◽  
Standard Diet ◽  
Vascular Endothelial ◽  
Pregnant Rats ◽  
Low Protein ◽  
Maternal Protein Restriction ◽  
Endothelial Growth Factor ◽  
Development Methods ◽  
Protein Diets

Background: Maternal protein restriction causes sperm alterations in the offspring, most of which are associated with epididymal functions. Because fluid reabsorption/secretion dynamics in the epididymal environment play important roles in the process of sperm maturation and concentration, we investigated the effects of maternal protein restriction on the expression of aquaporins (AQP1 and AQP9), vascular endothelial growth factor (VEGFa), and its receptor VEGFr-2 in different stages of postnatal epididymal development. Methods: Pregnant rats were divided into groups that received normoprotein (17% protein) and low-protein diets (6% protein) during gestation and lactation. After weaning, male rats only received the standard diet and were euthanized at the predetermined ages of 21, 44 and 120 days. Results: Maternal protein restriction decreased AQP1 and AQP9 expression in the initial segment and caput epididymis compared to the increased expression of these proteins observed in the corpus and cauda at all ages. Although protein restriction reduced the microvasculature density (MVD) on postnatal day (PND) 21 and 44, the MVD was unaltered on PND 120. Conclusions: Maternal protein restriction changed the structure or function of the offspring’s epididymis, specifically by affecting fluid dynamics and vasculogenesis in important stages of epididymis development.

Evaluation for cardiac toxicity with MRI in young adult survivors of acute lymphoblastic leukemia (ALL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18604-18604
Author(s):  
J. A. Wright ◽  
S. C. Reimold ◽  
N. J. Winick ◽  
A. Turoff ◽  
S. Brooks ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Young Adult ◽  
Cumulative Dose ◽  
Cardiac Mri ◽  
Cardiac Toxicity ◽  
Adult Survivors ◽  
Left Ventricular ◽  
Low Doses ◽  
Young Adult Survivors ◽  
Chi Square Analysis

18604 Background: Long-term survivors of childhood cancer treated with a moderate to high cumulative dose (≥300mg/m2) an anthracycline are known to be at risk for cardiac toxicity. It remains unclear what cardiac risk exists for survivors who received a low cumulative dose (<300mg/m2) of an anthracycline. Methods: We are conducting an NIH sponsored trial in 120 young adult survivors of ALL to determine the prevalence of cardiovascular risk factors and to determine the effectiveness of an exercise intervention. As part of their cardiovascular risk assessment, participants undergo cardiac MRI, a tool with excellent reproducibility in assessing left ventricular (LV) size and function. The aim of this component of the study is to determine the prevalence of cardiac toxicity in survivors treated with low dose anthracycline in comparison to those who did not receive any anthracycline. Descriptive statistics, chi-square analysis, and spearman correlation coefficients were used to examine the relationship between anthracycline dose and measures of cardiac function. Results: This study represents a work in progress. Preliminary results from the first 22 participants who have had a cardiac MRI do not show a significant difference in ejection fraction, LV mass, cardiac output, or mass to volume ratio between those treated with low cumulative dose anthracycline versus no anthracycline. Available cardiac MRI data for all participants will be presented at the meeting. Conclusions: With the continued use of an anthracycline at cumulative low doses, particularly in upcoming ALL standard risk trials, it is particularly important to determine if there is a risk of cardiac toxicity after low doses with aging. No significant financial relationships to disclose.

Profound cardioprotection with timolol in a female rat model of aging-related altered left ventricular function

2011 ◽  
Vol 89 (4) ◽  
pp. 277-288 ◽  
Author(s):  
Nazli N. Sozmen ◽  
Erkan Tuncay ◽  
Ayca Bilginoglu ◽  
Belma Turan
Keyword(s):  
Antioxidant System ◽  
Ventricular Myocytes ◽  
Heart Function ◽  
Thioredoxin Reductase ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Beneficial Effects ◽  
Age Related

Increasing evidence shows a marked beneficial effect with β-blockers in heart dysfunction via scavenging reactive oxygen species. Previously we showed that chronic treatment with either timolol or propranolol possessed similar beneficial effects for heart function in male rats as age increased, whereas only timolol exerted similar benefits in female rats. Therefore, in this study, we aimed first to examine the cellular bases for age-related alterations in excitation–contraction coupling in ventricular myocytes from female rats and, second, to investigate the hypothesis that age-related changes in [Ca2+]ihomeostasis and receptor-mediated system can be prevented with chronic timolol treatment. Chronic timolol treatment of 3-month-old female rats abolished age-related decrease in left ventricular developed pressure and the attenuated responses to β-adrenoreceptor stimulation. It also normalized the altered parameters of [Ca2+]itransients, decreased Ca2+loading of sarcoplasmic reticulum and increased basal [Ca2+]i, and decreased L-type Ca2+currents in 12-month-old female rats compared with the 3-month-old group. Adenylyl cyclase activity, β-adrenoreceptor affinity to its agonist, and β-adrenoreceptor density of the 12-month-old group are normalized to those of the 3-month-old group. Moreover, timolol treatment prevented dysfunction of the antioxidant system, including increased lipid peroxidation, decreased ratio of reduced glutathione to oxidized glutathione, and decreased activities of thioredoxin reductase and glucose-6-phosphate dehydrogenase, in the left ventricle of hearts from the 12-month-old group. Our data confirmed that aging-related early myocardial impairment is primarily related to a dysfunctional antioxidant system and impairment of Ca2+homeostasis, which can be prevented with chronic timolol treatment.

Nandrolone alter left ventricular contractility and promotes remodelling involving calcium-handling proteins and renin-angiotensin system in male SHR

Life Sciences ◽  
2018 ◽  
Vol 208 ◽  
pp. 239-245 ◽  
Author(s):  
Antonio F. Melo Junior ◽  
Polyana L.M. Dalpiaz ◽  
Glauciene J. Sousa ◽  
Phablo Wendell C. Oliveira ◽  
Antônio M. Birocale ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Calcium Handling Proteins

Abstract 269: Cardiac Aging in Rats: Do Female and Male Hearts Age Differently?

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Eduard I Dedkov ◽  
Alessandro Pingitore
Keyword(s):  
Experimental Studies ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Laboratory Animals ◽  
Cardiac Aging ◽  
Male And Female ◽  
Male And Female Rats ◽  
Significant Difference ◽  
Systolic Performance

Background: In recent years, the use of middle-aged and old animals of both sexes has become preferential in experimental studies involving the models of cardiovascular diseases to better reflect a human population. However, the evidence showing the extent of sex-related differences in cardiac aging of laboratory animals remains obscure. Accordingly, we designed our study to determine whether the male and female rats differ during aging with regard to left ventricular (LV) geometry and systolic function. Methods: We performed transthoracic echocardiographic examinations in 12-month-old (12mo) and 24 month-old (24mo) male and female Sprague-Dawley rats (Charles River, Wilmington, MA) under 1.5% isoflurane anesthesia using a linear (Matrix) array transducer probe GE M12L (5.5-14.0 MHz) and a GE Vivid 7 Dimension ultrasound system. Two-dimensional short-axis views and M-mode tracings of the LV at the papillary muscle level were recorded and used to estimate various LV parameters. Results: We found that 24mo-Female rats had a significant increase in LV chamber dimensions associated with a reduction in its systolic performance as compared to 12mo-Female rats (Table 1). In contrast, LV parameters remained similar between 12mo- and 24mo-Male rats. Table 1. Echocardiographic parameters of LV chamber geometry and systolic performance Values are means ± SE. Arrow indicates a significant difference between age groups ( P ≤ 0.05). Conclusion: Our data demonstrate that during cardiac aging female rats have a different pattern of LV changes compared to males that must be considered in the design of future experimental studies.

scholarly journals Sex differences in depression-like behavior and neuroinflammation in rats post-MI: role of estrogens

2018 ◽  
Vol 315 (5) ◽  
pp. H1159-H1173 ◽  
Author(s):  
Fatimah Najjar ◽  
Monir Ahmad ◽  
Diane Lagace ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Sex Differences ◽  
Prefrontal Cortex ◽  
Young Adult ◽  
Female Rats ◽  
Male Rats ◽  
Mild Depression ◽  
Cytokine Levels ◽  
17Β Estradiol

Patients with heart failure (HF) have a high prevalence of depression associated with a worse prognosis, particularly in older women. The present study evaluated whether sex and estrogens affect depression-like behavior and associated neuroinflammation induced by myocardial infarction (MI) in rats. MI was induced by occlusion of the left anterior descending artery in young adult male and female Wistar rats or in ovariectomized (OVX) female rats without and with estrogen [17β-estradiol (E2)] replacement. MI groups showed a comparable degree of cardiac dysfunction. Eight weeks post-MI, male rats with HF exhibited depression-like behaviors, including anhedonia and higher immobility in the sucrose preference and forced swim tests, which were not observed in female rats with HF. In the cued fear conditioning test, male but not female rats with HF froze more than sham rats. After OVX, female sham rats developed mild depression-like behaviors that were pronounced in OVX female rats post-MI and were largely prevented by E2 replacement. Cytokine levels in the plasma and paraventricular nucleus increased in both sexes with HF, but only male rats with HF showed an increase in cytokine levels in the prefrontal cortex. OVX alone did not affect cytokine levels, but OVX-MI caused significant increases in the prefrontal cortex, which were shifted to an anti-inflammatory pattern by E2 replacement. These results suggest that estrogens prevent depression-like behavior induced by HF post-MI in young adult female rats by inhibiting proinflammatory cytokine production and actions in the prefrontal cortex. NEW & NOTEWORTHY In contrast to male rats, female rats with heart failure after myocardial infarction do not develop depression-like behavior or increases in prefrontal cortex cytokines. However, after ovariectomy, female rats exhibit similar changes, which are prevented by 17β-estradiol replacement. Neuroinflammation in the prefrontal cortex in male subjects may contribute to depression-like behavior, whereas its estrogen-dependent absence in female subjects may protect against depression. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/sex-differences-in-depression-like-behavior-post-myocardial-infarction/ .

Distinct gene-sex interactions regulate adult rat cardiomyocyte width and length independently

2002 ◽  
Vol 12 (1) ◽  
pp. 61-67 ◽  
Author(s):  
I. Boutin-Ganache ◽  
S. Picard ◽  
C. F. Deschepper
Keyword(s):  
Genetic Linkage ◽  
Ventricular Hypertrophy ◽  
Inbred Strains ◽  
Left Ventricular ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rat ◽  
Peptide Precursor ◽  
Wistar Kyoto ◽  
Peptide Product

Wistar-Kyoto (WKY) and WKY-derived hyperactive (WKHA) rats are two genetically-related inbred strains of rats that are both normotensive yet exhibit differences in left ventricular mass (LVM). We had shown previously that cardiomyocytes from male WKHA are wider than that of male WKY, and that there was genetic linkage between LVM and a locus on chromosome 5 (RNO5) in the male progeny of a F2 WKHA/WKY cross. We show here that cardiomyocyte width is linked to the same RNO5 locus in male reciprocal congenic rats derived from WKHA and WKY. Contrary to males, we found no genetic linkage between LVM and the RNO5 locus in female rats. However, ventricular hypertrophy in females might be of a different nature, because cardiomyocytes from female WKHA were shorter than their WKY counterparts (with no difference in width). The RNO5 locus contains that of the natriuretic peptide precursor A (Nppa) gene. In male congenic rats, changes in cardiomyocyte width always correlated with reciprocal changes in the LV concentration of atrial natriuretic factor (ANF, i.e., the peptide product of Nppa). Taken together with other functional data, the small size of the RNO5 locus (∼63 cR) increased the likelihood that both cardiomyocyte width and LV ANF concentration could be linked to only one gene (possibly Nppa) in male rats. Moreover, our results support the notion that genes and sex interact to regulate cardiomyocyte width and length independently from one another.

Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats

2005 ◽  
Vol 288 (1) ◽  
pp. R34-R38 ◽  
Author(s):  
Amanda J. Drake ◽  
Brian R. Walker ◽  
Jonathan R. Seckl
Keyword(s):  
Cardiovascular Risk ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Fetal Programming ◽  
First Generation ◽  
Epidemiological Studies ◽  
Female Rats ◽  
Male Rats ◽  
Fetal Life ◽  
Gluconeogenic Enzyme

Epidemiological studies linking low birth weight and subsequent cardiometabolic disease have given rise to the hypothesis that events in fetal life permanently program subsequent cardiovascular risk. The effects of fetal programming may not be limited to the first-generation offspring. We have explored intergenerational effects in the dexamethasone-programmed rat, a model in which fetal exposure to excess glucocorticoid results in low birth weight with subsequent adult hyperinsulinemia and hyperglycemia underpinned by increased activity of the key hepatic gluconeogenic enzyme, phospho enolpyruvate carboxykinase (PEPCK). We found that the male offspring of female rats that had been exposed prenatally to dexamethasone, but were not manipulated in their own pregnancy, also had reduced birth weight (5.66 ± 0.06 vs. 6.12 ± 0.06 g, P < 0.001), glucose intolerance, and elevated hepatic PEPCK activity (5.7 ± 0.6 vs. 3.3 ± 0.2 nmol·min−1·mg protein−1, P < 0.001). These effects resolved in a third generation. Similar intergenerational programming was observed in offspring of male rats exposed prenatally to dexamethasone mated with control females. The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the “programming phenotype” and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.

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