Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

scholarly journals The effect of a myocardial infarction on the normalized time-varying elastance curve

2007 ◽  
Vol 102 (3) ◽  
pp. 1123-1129 ◽  
Author(s):  
David Jegger ◽  
Ajit S. Mallik ◽  
Mohammed Nasratullah ◽  
Xavier Jeanrenaud ◽  
Rafaela da Silva ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Output ◽  
Coronary Artery ◽  
Control Group ◽  
Time Varying ◽  
Conductance Catheter ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Heart Cycle ◽  
Isovolumic Relaxation

It has been suggested that the shape of the normalized time-varying elastance curve [En( tn)] is conserved in different cardiac pathologies. We hypothesize, however, that the En( tn) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats ( n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) ( n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the En( tn) derived. Slopes of En( tn) during the preejection period (αPEP), ejection period (αEP), and their ratio (β = αEP/αPEP) were calculated, together with the characteristic decay time during isovolumic relaxation (τ) and the normalized elastance at end diastole (Eminn). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (−33%), ejection fraction (−40%), and stroke volume (−30%) ( P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 ± 0.31 mmHg/μl (CTRL) to 0.34 ± 0.11 mmHg/μl (MI) ( P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods ( P < 0.05). The slope of En( tn) during the αPEPand β were significantly altered after MI ( P < 0.05). Furthermore, τ and end-diastolic Eminnwere both significantly augmented in the MI group. We conclude that the En( tn) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

Chronotropic, Inotropic and Dromotropic Parameters of the Heart and Oxidative Stress in Rats Receiving High Doses of Fructose

2019 ◽  
Vol 8 ◽  
pp. 1250
Author(s):  
Esmat Radmanesh ◽  
Mahin Dianat ◽  
Narges Atefipour
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Drinking Water ◽  
Control Group ◽  
Free Access ◽  
Qtc Interval ◽  
Sprague Dawley ◽  
Cvd Risk ◽  
Sprague Dawley Rats ◽  
High Doses

Background: Many risk factors, including nutritional ones, contribute to cardiovascular diseases (CVDs). Increased fructose consumption, for example, can lead to an increase in CVD risk factors, i.e. an increase in blood lipids and the development of insulin resistance. Materials and Methods: In the present study, Sprague Dawley rats were divided into two groups:  control group (free access to tap drinking water for seven weeks), and a group that received fructose 10% in drinking water for seven weeks, (n ═8 per each group). In all groups, before starting the test period and seven weeks after it, electrocardiogram was recorded by Power lab system. Unpaired t-test and two-way ANOVA were used for data analysis. Also, oxidative stress parameters were measured. Results: In the group received high doses of fructose, a significant reduction (P <0.05) was observed in the PR interval (P<0.001) and a significant increase (P<0.05) in the QTc interval. However, there was no significant change in the RR interval and the voltage of the QRS complex. A significant decrease in catalase, superoxide dismutase and glutathione peroxidase (P<0.05) and a significant increase (P<0.05) in malondialdehyde and lactate dehydrogenase were observed in the group that received fructose in comparison with the control group at the end of the experiment. Conclusion: According to our results, the chance of arrhythmias in the rats receiving high doses of fructose was possibly due to the increased oxidative stress in the healthy rats. [GMJ.2019;8:e1250]

scholarly journals Dietary Supplementation with Chitosan Oligosaccharides Alleviates Oxidative Stress in Rats Challenged with Hydrogen Peroxide

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 55 ◽  
Author(s):  
Ruixia Lan ◽  
Qingqing Chang ◽  
Lilong An ◽  
Zhihui Zhao
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Drinking Water ◽  
Dietary Supplementation ◽  
Basal Diet ◽  
Control Group ◽  
Sprague Dawley ◽  
Antioxidant Power ◽  
Chitosan Oligosaccharides ◽  
Sprague Dawley Rats

Oxidative stress is induced by excessive oxidative radicals, which directly react with biomolecules, and damage lipids, proteins and DNA, leading to cell or organ injury. Supplementation of antioxidants to animals can be an effective way to modulate the antioxidant system. Chitosan oligosaccharides (COS) are the degraded products of chitosan or chitin, which has strong antioxidant, anti-inflammatory, and immune-enhancing competency. Therefore, the current study was conducted to evaluate the hypothesis that dietary supplementation with COS alleviates the damage caused by oxidative stress in Sprague Dawley rats challenged with hydrogen peroxide (H2O2). The rats were randomly divided into three groups: CON, control group, in which rats were fed a basal diet with normal drinking water; AS, H2O2 group, in which rats were fed the basal diet and 0.1% H2O2 in the drinking water; ASC, AS + COS group, in which rats were fed the basal diet with 200 mg/kg COS, and with 0.1% H2O2 in the drinking water. In vitro, COS exhibited better radical scavenging capacity of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O2−), H2O2, and ferric ion reducing antioxidant power (FRAP) than butylated hydroxy anisole (BHA). In vivo, dietary supplementation with COS alleviated the H2O2-induced oxidative damage, evidenced by comparatively increasing activity of SOD, CAT, GSH-Px, GSH, and T-AOC, and comparatively decreasing level of MDA in serum, liver, spleen, and kidney. COS also comparatively alleviated the H2O2-induced inflammation. In conclusion, COS supplementation reduced lipid peroxidation and restored antioxidant capacity in Sprague Dawley rats, which were challenged with H2O2.

scholarly journals Cardioprotective effect of lithium chloride on a rat model of myocardial infarction

2019 ◽  
Vol 23 (2) ◽  
pp. 43 ◽  
Author(s):  
O. A. Grebenchikov ◽  
A. V. Lobanov ◽  
E. R. Shayhutdinova ◽  
A. N. Kuzovlev ◽  
A. V. Ershov ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Lithium Chloride ◽  
Rat Model ◽  
Conflict Of Interest ◽  
Chloride Solution ◽  
Glycogen Synthase ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Lithium Chloride Solution

<p><strong>Aim.</strong> To investigate the cardioprotective effect of lithium chloride in vivo on a rat model of myocardial infarction.<br /><strong>Methods.</strong> Twelve male Sprague-Dawley rats were randomly divided into two groups of six, with both groups modelling cardiac ischaemia and subsequent reperfusion. At the start of reperfusion, 30 mg/kg of 4.2% lithium chloride solution was intravenously administered via a catheter to the test group and 0.5 ml/kg of saline solution was administered to the comparison group. A control group comprised sham-operated rats that were not injected with any drugs other than anaesthesia during making skin incision. At the end of each experiment, the total area of the risk zone and areas of the infarction zone and left ventricle were calculated for each animal using a double-staining technique with 2% methylene blue and 1% triphenyltetrazolium chloride. A further series of experiments using 15 male Sprague-Dawley rats (third group) was performed to assess the protein content of glycogen synthase-3β in myocardial tissue. The method was similar to that for the earlier experiments; however, at the end of the experiments, the hearts were removed and homogenised, following which the concentration of glycogen synthase-3β was determined using electrophoresis.<br /><strong>Results.</strong> The group treated with lithium chloride showed a significant decrease in the area of the infarction zone compared with the group treated with saline. The difference in the indices between the two groups was &gt;26% (p &lt; 0.05).<br /><strong>Conclusion.</strong> This study demonstrated that 30 mg/kg of 4.2% lithium chloride solution, administered at the onset of reperfusion, exerted a protective effect on cardiomyocytes in a rat model of myocardial infarction by reducing the area of the infarction zone compared with that in the control group. This effect was probably mediated by an almost two-fold increase in the content of the phosphorylated form of glycogen synthase-3β in the myocardium.</p><p>Received 23 June 2019. Revised 6 August 2019. Accepted 7 August 2019.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p><p><strong>Author contributions</strong> <br />Conception and study design: A.N. Kuzovlev<br />Data collection and analysis: O.A. Grebenchikov<br />Statistical analysis: A.V. Ershov<br />Drafting the article: A.V. Lobanov, E.R. Shayhutdinova<br />Critical revision of the article: V.V. Likhvantsev<br />All authors approved final version to be published.<br /><br /></p>

scholarly journals Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 653
Author(s):  
Shuxia Jiang ◽  
Taining Guo ◽  
Shihui Guo ◽  
Jiang Gao ◽  
Yingdong Ni ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Damage ◽  
Weight Ratio ◽  
Luciferase Reporter ◽  
Control Group ◽  
Hepatic Iron ◽  
Sprague Dawley ◽  
Reporter System ◽  
Sprague Dawley Rats ◽  
Chronic Variable Stress

It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.

scholarly journals The effect of aspartame and sucralose intake on body weight measures and blood metabolites: role of their form (solid and/or liquid) of ingestion

2021 ◽  
pp. 1-21
Author(s):  
M.E. Ragi ◽  
R. El-Haber ◽  
F. El-Masri ◽  
O.A. Obeid
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Caloric Intake ◽  
Blood Metabolites ◽  
Control Group ◽  
Plain Water ◽  
Free Access ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Access To Food

Abstract The ingestion of non-caloric sweeteners from food and/or drink was intended to reduce caloric intake without compromising palatability. However, the inconclusive relation between non-caloric sweeteners and body weight may partially relate to their form of ingestion (solid or liquid). Thus, two paralleled experiments (Aspartame and Sucralose) were conducted. In each, Sprague Dawley rats (7-week-old male) were randomly divided into 4 groups. In experiment 1, aspartame (0.05%) was added to the diet (AD) or drinking water (AW) or both diet and water (ADW), and a control group (C) was given a non-sweetened diet with plain water. In experiment 2, sucralose (0.016%) was similarly provided in the diet (SD) or drinking water (SW) or both diet and water (SDW), with a control group (C). All rats had free access to food and water for 7 weeks. Energy intake, body weight, and body composition were monitored and blood metabolites were determined. Results showed that aspartame ingestion significantly increased body weight and fat mass mainly due to an increase in energy efficiency. The effect was related to the amount rather than the form of ingestion. Additionally, aspartame ingestion was associated with glucose intolerance. Sucralose ingestion had a similar impact to that of aspartame though to a lesser extent. In conclusion, 7-week ingestion of aspartame and sucralose had adverse effects on body measures that were not related to the form of ingestion.

scholarly journals Metabonomic Strategy to the Evaluation of Chinese Medicine Compound Danshen Dripping Pills Interfering Myocardial Ischemia in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xue Xin ◽  
Haimiao Zou ◽  
Ningning Zheng ◽  
Xinchun Xu ◽  
Yinmin Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chinese Medicine ◽  
Sham Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Metabolic Pattern ◽  
Great Achievement ◽  
Sprague Dawley Rats ◽  
Therapeutic Mechanism ◽  
Metabolic Biomarkers

Coronary heart disease (CHD) is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs) have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d). The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA) models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

scholarly journals Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

2021 ◽  
Vol 18 (4) ◽  
pp. 1645
Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Endurance Exercise ◽  
Field Tests ◽  
Treadmill Running ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

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