Hypertension and Cardiac Hypertrophy in Growth Hormone-Deficient Rats

1. Growth hormone may influence cardiac growth during post-natal maturation or in response to hypertension, and the growth-hormone deficient dwarf rat model offers an opportunity to study this question. 2. We compared the blood pressure and heart weight of dwarf rats and Fischer (F344) control rats in early adulthood, after two hypertensive stimuli: unilateral renal ischaemia (two-kidney, one-clip) or the administration of deoxycorticosterone acetate and saline drinking fluid. 3. In untreated animals at 13 weeks of age the body weight of dwarf rats was significantly less than that of F344 rats, but the mean arterial pressure was similar. Although the hearts of dwarf rats were smaller than those of F344 rats, the heart weight/body weight ratio was significantly greater in dwarf rats. 4. Both dwarf and F344 rats developed similar hypertensive mean arterial pressures 5 weeks after left renal artery clipping or treatment with deoxycorticosterone acetate salt. The heart weights of hypertensive dwarf and F344 rats were equivalent, indicating a proportionally greater increase in cardiac size in dwarf rats for the same rise in blood pressure. 5. The plasma insulin-like growth factor-I level was markedly lower in dwarf than in F344 rats, and hypertension did not have any significant effects on these levels. 6. These findings indicate that the developmental increase in blood pressure and heart size in growing animals and the adaptive cardiac hypertrophy accompanying hypertension are not affected by growth hormone deficiency.

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Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7856318 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Soheb Anwar Mohammed ◽

Bugga Paramesha ◽

Yashwant Kumar ◽

Ubaid Tariq ◽

Sudheer Kumar Arava ◽

...

Keyword(s):

Body Weight ◽

Cardiac Hypertrophy ◽

Weight Ratio ◽

Chronic Administration ◽

The Body ◽

Heart Weight ◽

Serum Biochemical ◽

Enalapril Treatment ◽

Histopathological Investigation

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.

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PO-148 Effect of Aerobic Exercise on the Expression of CaMKIIδ/MEF2 in Hypertensive and Physiological Cardiac Hypertrophy

Exercise Biochemistry Review ◽

10.14428/ebr.v1i4.10513 ◽

2018 ◽

Vol 1 (4) ◽

Author(s):

Man Zhu ◽

Lijun Shi

Keyword(s):

Body Weight ◽

Cardiac Hypertrophy ◽

Aerobic Exercise ◽

Weight Ratio ◽

Exercise Group ◽

The Body ◽

Expression Level ◽

Heart Weight ◽

Control Group ◽

Body Weight Ratio

Objective The type II calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) signal plays a key role in the development of cardiac hypertrophy. This study used CaMKIIδ as an entry point to investigate the mechanism of moderate-intensity aerobic exercise affecting myocardial function. Methods Male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs), 12 weeks age, were randomly divided into aerobic exercise group (SHR-EX/WKY-EX) and sedentary control group (SHR-SED/WKY-SED), with 12 rats in each group. The aerobic exercise group conducted an 8-week treadmill exercise training with a slope of 0°, 20m/min (about 55-65% of maximal aerobic velocity), 60min/day, and 5d/wk. The control group did not exercise. The body weight of each group of rats was measured weekly and the blood pressure of the rats was measured non-invasively. After 8 weeks, the hearts of SHR-EX group, WKY-EX group, SHR-SED group and WKY-SED group were weighed, and then myocardial tissue sections were taken for HE staining to observe the thickness of the ventricular wall and the morphology of myocardial cells. The expression of CaMKIIδ and MEF2 in each group was determined by Western blotting. Results (1) The body weight of SHR-SED group was significantly higher than that of SHR-EX group (p<0.01), and the heart weight of rats in exercise group changed significantly. The WKY-EX group had greater heart weight than the WKY-SED group, and the SHR-SED group was heavier than the SHR-EX group (p<0.05). The heart weight/body weight ratio of the WKY-EX group was significantly higher than that of the WKY-SED group (p<0.01). The heart weight/body weight ratio of SHR-EX group and SHR-SED group was higher than that of WKY-EX group and WKY-SED group (p<0.01). (2) Compared with the WKY-SED group, the SHR-SED group had loose interstitial cells and increased single cell area. The SHR-EX group is more compact than the SHR-SED group, and the cell cross-sectional area is reduced. (3) The expression of CaMKIIδ protein in SHR-EX group was significantly lower than that in SHR-SED group (p<0.01), but the expression level of CaMKIIδ in WKY-EX group was significantly higher than that in WKY-SED group (p<0.01). The expression level of CaMKIIδ was significantly higher in the SHR-SED group than in the WKY-SED group. In addition, the expression of MEF2 protein in SHR-EX group and WKY-SED group was significantly lower than that in SHR-SED group (p<0.01), while the MEF2 expression level in WKY-EX group was higher than WKY-SED group and SHR-EX group (p<0.05). Conclusions There is an interaction between aerobic exercise and hypertension. Aerobic exercise can effectively delay the development of hypertensive cardiac hypertrophy by regulating the expression of CaMKIIδ and MEF2 protein in the myocardium, but it can also cause cardiac hypertrophy in normal heart. It is one of the important mechanisms affecting the myocardial morphology and function.

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Abstract 13798: Ablation of the Hypertension Candidate Gene ATP2B1 Results in Increased Blood Pressure and Cardiac Hypertrophic Remodeling

Circulation ◽

10.1161/circ.130.suppl_2.13798 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sally K Hammad ◽

Min Zi ◽

Sukhpal Prehar ◽

Robert Little ◽

Ludwig Neyses ◽

...

Keyword(s):

Blood Pressure ◽

Cardiac Hypertrophy ◽

Diastolic Pressure ◽

Association Studies ◽

Weight Ratio ◽

Blood Pressure Regulation ◽

Heart Weight ◽

Genome Wide Association Studies ◽

Pressure Regulation ◽

The Impact

Introduction: Hypertension is a major risk factor for cardiac hypertrophy and heart failure. Genome wide association studies have recently identified single nucleotide polymorphisms in ATP2B1 , the gene encoding the calcium extrusion pump, plasma membrane calcium ATPase (PMCA1), as having a strong association with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: We aim to examine whether there is a functional link between PMCA1 and blood pressure regulation, and the development of hypertension. And to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1 we generated a global PMCA1 heterozygous knockout mouse (PMCA1 Ht ). PMCA1 Ht mice had 46% to 52% reduction in PMCA1 protein expression compared to the WT, in aorta, heart, kidney and brain. To study the mice under hypertensive stress conditions, 3 month old PMCA1 Ht and wild type (WT) mice were infused via minipump with angiotensin II (1mg/Kg/daily) or water as a control. Upon angiotensin treatment, PMCA1 Ht mice showed a significantly greater increase in systolic (62.24±3.05 mmHg) and diastolic pressure (52.68±4.67 mmHg), in comparison to the WT (33.37±2.91 mmHg and 23.94±4.56 mmHg, respectively), P<0.001, n=12. Moreover, PMCA1 Ht mice showed a significantly greater hypertrophic response as indicated by a greater heart weight to tibia length ratio, cardiomyocyte cell size (410±18.7 μm 2 ), compared to WT mice (340.4±9.8 μm 2 ), and increased expression of B-type natriuretic peptide (BNP), 2.36 ± 0.25 fold change, n =5-6, P< 0.01. Echocardiography showed no significant changes between PMCA1 Ht and WT mice, in heart rate, and in cardiac function, as indicated by fractional shortening and ejection fraction. In addition, PMCA1 Ht mice showed no sign of lung congestion as indicated by lung weight to body weight ratio. Conclusion: ATP2B1 deletion leads to increased blood pressure and cardiac hypertrophy. This provides functional evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

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Abstract 670: Immediate And Sustained Blood Pressure Lowering by CRF-receptor Stimulation: A Novel Approach To Antihypertensive Therapy?

Circulation ◽

10.1161/circ.116.suppl_16.ii_124-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Thomas Dieterle ◽

Silvia Meili-Butz ◽

Katrin Buehler ◽

Christian Morandi ◽

Dietlinde John ◽

...

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Arterial Hypertension ◽

Weight Ratio ◽

Chronic Administration ◽

Cardiovascular Responses ◽

High Salt ◽

Heart Weight ◽

Receptor Stimulation ◽

Novel Approach

Background: Recently, novel corticotropin-releasing factor (CRF)-related peptides, named urocortin I (UcnI), UcnII, and UcnIII were described. Available data suggest that the Ucns are part of a peripheral CRF system modulating cardiovascular function and mediating cardiovascular responses to stress. Blood pressure (BP) lowering effects have been described after administration of UcnI. However, no data are available on effects of UcnII on BP in an animal model of systemic arterial hypertension. Methods: Experiments were performed in Dahl salt-sensitive (DSS) and salt-resistant rats (DSR, control). Animals were fed a diet containing 4% NaCl (high salt) to induce arterial hypertension in DSS rats. At the end of week 2 of high salt diet, both DSS and DSR rats were randomly assigned to i.p. injections of either UcnII (2.5 μg/kg body weight) or vehicle b.i.d. for five weeks. Animals underwent repetitive tail cuff BP measurements at baseline (prior to first injection), at 5 and 15 minutes after the first injection and at week 1, 2, and 5 of b.i.d. treatment. At week 5 animals were sacrificed to determine heart weight /body weight ratio. Results: Systolic BP (SBP, mmHg) and heart rate (HR, min −1 ) are given in the following table as mean ± SD (n=10 per group). Conclusions: In hypertensive DSS rats, acute CRF-receptor stimulation by UcnII immediately lowered BP to the range observed in DSR rats. Compared to vehicle-treated DSS rats, sustained BP reduction was observed with further chronic administration of UcnII. No severe reflex tachycardia was observed after administration of UcnII. Thus, CRF-receptor stimulation might represent a novel approach to the treatment of arterial hypertension.

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Studies of Body Weight/Heart Weight [C/S] Ratio in Treated and Untreated Experimental Pulmonary Barotrauma

Polish Hyperbaric Research ◽

10.2478/phr-2019-0020 ◽

2019 ◽

Vol 69 (4) ◽

pp. 63-70

Author(s):

Piotr Siermontowski ◽

Wojciech Kozłowski ◽

Katarzyna Pleskacz

Keyword(s):

Body Weight ◽

Weight Ratio ◽

Total Body Weight ◽

External Pressure ◽

The Body ◽

Heart Weight ◽

Control Group ◽

Pulmonary Barotrauma ◽

Pulmonary Parenchyma ◽

Sudden Decrease

AbstractThe prerequisite of development of pulmonary barotrauma [PB] is retention of the breathing mix in the lungs during a sudden decrease in external pressure or its administration into the airways under increased pressure or in a volume exceeding the maximum lung capacity. In such cases, the pulmonary parenchyma ruptures and air enters both the pleural cavity and/or the lumen of ruptured blood vessels located in the alveolar septa. The result is permanent disruption of the pulmonary parenchyma.The aim of the study was to assess the influence of post-PB lesions on the heart muscle and the importance of hyperbaric treatment on the exacerbation of such lesions in the heart. The hearts of 35 rabbits were used in the study. In animals of the experimental group, PB was induced in the pressure chamber using the proprietary method described in previous publications. Part of the animals in this group were treated with air hyperbaria. The comparison group consisted of animals, which did not undergo PB during a simulated dive. All animals were weighed, observed for four weeks and then put to death following the experiment. In autopsy, among others, whole hearts were collected and weighed after fixation. Subsequently, the C/S ratio, i.e. the body to heart weight ratio, was calculated. The measurement results were subject to statistical analysis. A statistically significant increase in the C/S ratio was found, indicating an increase in the share of heart weight in the total body weight in the group of animals with PB not treated with air hyperbaria as compared to the control group.

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Cardioprotective Effects of the Novel Compound Vastiras in a Preclinical Model of End-Organ Damage

Hypertension ◽

10.1161/hypertensionaha.120.14704 ◽

2020 ◽

Vol 75 (5) ◽

pp. 1195-1204

Author(s):

Raffaele Altara ◽

Gustavo J.J. da Silva ◽

Michael Frisk ◽

Francesco Spelta ◽

Fouad A. Zouein ◽

...

Keyword(s):

Blood Pressure ◽

Cardiac Hypertrophy ◽

Natriuretic Peptide ◽

Renal Damage ◽

Weight Ratio ◽

Hypertensive Heart Disease ◽

Heart Weight ◽

Preclinical Model ◽

Continuous Administration ◽

Positive Effects

Cardiac hypertrophy and renal damage associated with hypertension are independent predictors of morbidity and mortality. In a model of hypertensive heart disease and renal damage, we tested the actions of continuous administration of Vastiras, a novel compound derived from the linear fragment of ANP (atrial natriuretic peptide), namely pro-ANP 31–67 , on blood pressure and associated renal and cardiac function and remodeling. Of note, this peptide, unlike the ring structured forms, does not bind to the classic natriuretic peptide receptors. Dahl/Salt–Sensitive rats fed a 4% NaCl diet for 6 weeks developed hypertension, cardiac hypertrophy, and renal damage. Four weeks of treatment with 50 to 100 ng/kg per day of Vastiras exhibited positive effects on renal function, independent of blood pressure regulation. Treated rats had increased urine excretion, natriuresis, and enhanced glomerular filtration rate. Importantly, these favorable renal effects were accompanied by improved cardiac structure and function, including attenuated cardiac hypertrophy, as indicated by decreased heart weight to body weight ratio, relative wall thickness, and left atrial diameter, as well as reduced fibrosis and normalized ratio of the diastolic mitral inflow E wave to A wave. A renal subtherapeutic dose of Vastiras (25 ng/kg per day) induced similar protective effects on the heart. At the cellular level, cardiomyocyte size and t-tubule density were preserved in Vastiras-treated compared with untreated animals. In conclusion, these data demonstrate the cardiorenal protective actions of chronic supplementation of a first-in-class compound, Vastiras, in a preclinical model of maladaptive cardiac hypertrophy and renal damage induced by hypertension.

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Genistein prevents isoproterenol-induced cardiac hypertrophy in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y2012-068 ◽

2012 ◽

Vol 90 (8) ◽

pp. 1117-1125 ◽

Cited By ~ 21

Author(s):

Subir Kumar Maulik ◽

Pankaj Prabhakar ◽

Amit Kumar Dinda ◽

Sandeep Seth

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Body Weight ◽

Nitric Oxide Synthase ◽

Cardiac Hypertrophy ◽

Weight Ratio ◽

Left Ventricular ◽

Heart Weight ◽

Once Daily ◽

Oxide Synthase

Genistein, an isoflavone and a rich constituent of soy, possesses important regulatory effects on nitric oxide (NO) synthesis and oxidative stress. Transient and low release of NO by endothelial nitric oxide synthase (eNOS) has been shown to be beneficial, while high and sustained release by inducible nitric oxide synthase (iNOS) may be detrimental in pathological cardiac hypertrophy. The present study was designed to evaluate whether genistein could prevent isoproterenol-induced cardiac hypertrophy in male Wistar rats (150–200 g, 10–12 weeks old) rats. Isoproterenol (5 mg·(kg body weight)–1) was injected subcutaneously once daily for 14 days to induced cardiac hypertrophy. Genistein (0.1 and 0.2 mg·kg–1, subcutaneous injection once daily) was administered along with isoproterenol. Heart tissue was studied for myocyte size and fibrosis. Myocardial thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase levels, and 1-OH proline (collagen content) were also estimated. Genistein significantly prevented any isoproterenol-induced increase in heart weight to body weight ratio, left ventricular mass (echocardiographic), myocardial 1-OH proline, fibrosis, myocyte size and myocardial oxidative stress. These beneficial effects of genistein were blocked by a nonselective NOS inhibitor (L-NAME), but not by a selective iNOS inhibitor (aminoguanidine). Thus, the present study suggests that the salutary effects of genistein on isoproterenol-induced cardiac hypertrophy may be mediated through inhibition of iNOS and potentiation of eNOS activities.

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Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism

Frontiers in Pharmacology ◽

10.3389/fphar.2021.653901 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoying Zhang ◽

Zhiying Zhang ◽

Pengxiang Wang ◽

Yiwei Han ◽

Lijun Liu ◽

...

Keyword(s):

Body Weight ◽

Energy Metabolism ◽

Cardiac Hypertrophy ◽

Heart Function ◽

Weight Ratio ◽

Tibetan Medicine ◽

Heart Weight ◽

Cardiomyocyte Hypertrophy ◽

Body Weight Ratio ◽

Cross Sectional

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.

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Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

Cardiovascular Research ◽

10.1093/cvr/cvz016 ◽

2019 ◽

Vol 116 (1) ◽

pp. 101-113 ◽

Cited By ~ 4

Author(s):

Hairuo Lin ◽

Yang Li ◽

Hailin Zhu ◽

Qiancheng Wang ◽

Zhenhuan Chen ◽

...

Keyword(s):

Heart Failure ◽

Body Weight ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Weight Ratio ◽

Left Ventricular ◽

Neonatal Rat ◽

Cardiac Remodelling ◽

Heart Weight ◽

Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

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The HDAC Inhibitor Emodin Blocks Hypertension-Induced Cardiac Hypertrophy: A Mediating Role for the Gut?

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_029 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 396-396

Author(s):

Levi Evans ◽

Brad Ferguson

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Cardiac Hypertrophy ◽

Parent Compound ◽

Heart Weight ◽

Female Mice ◽

Blood Institute ◽

Mediating Role ◽

Funding Sources ◽

Pathological Cardiac Hypertrophy

Abstract Objectives Evidence suggests that food bioactives impact the epigenome to prevent pathological cardiac hypertrophy. Recently, we showed that emodin, an anthraquinone, attenuated pathological cardiac hypertrophy and histone deacetylase (HDAC) activity. However, we only examined the cardioprotective effects of emodin's parent compound, not of emodin metabolites or of emodin-gut microbiome interactions. The microbiome has emerged as a key player in chronic diseases such as metabolic and cardiac disease. Thus, we hypothesized that emodin could reverse hypertension-induced changes in microbial communities. Methods Normo- and hypertensive (angiotensin ii) C57/BL6 female mice were randomly assigned to receive vehicle (Veh, DMSO: PEG 1:1) or emodin (Emod, 30 mg/kg) for 14 days. Body weight was collected pre- and post-treatment and blood pressure assessed via tail-cuff. At study end, mice were euthanized and assessed for heart weight and fibrosis. In addition, stool samples and cecal content were collected to elucidate changes in microbial populations using 16S rRNA sequencing. Lastly, tissue was lysed and RNA isolated for RNA sequencing. One-way ANOVA with Tukey's post-hoc was performed unless otherwise specified and P < 0.05 considered significant. Results Emodin significantly attenuated cardiac hypertrophy and fibrosis in female mice. No significant changes were observed for body weight or systolic blood pressure in response to hypertension or emodin. Lastly, preliminary analysis suggests that hypertension altered the microbiome, with evidence to support that emodin effects gut microbiota. Conclusions Our data demonstrates that emodin attenuates pathological hypertrophy and fibrosis in female mice. Whether this attenuation in cardiac remodeling is driven, in part, by the actions of emodin on the gut the microbiome remains unclear and is currently an active topic of investigation in our lab. Funding Sources This work is supported by the USDA NIFA (Hatch-NEV00767), the Dennis Meiss & Janet Ralston Fund for Nutri-epigenetic Research, the National Institute for General Medical Sciences (NIGMS) of the NIH (P20 GM130459) and the National Heart, Lung, and Blood Institute of the NIH (R15 HL143496) to B.S.F. Core facilities used for Research were supported by NIGMS of the NIH (P20 GM103554).

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