scholarly journals Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

2016 ◽  
Vol 39 (1) ◽  
pp. 229-241 ◽  
Author(s):  
Jian Yang ◽  
Yu-Ning Chen ◽  
Zao-Xian Xu ◽  
Yun Mou ◽  
Liang-Rong Zheng
Keyword(s):  
Cardiac Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Heart Weight ◽  
Farnesyl Pyrophosphate ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Aortic Remodeling

Background: In our previous study, farnesyl pyrophosphate synthase (FPPS) was shown to be increased in spontaneously hypertensive rats (SHR) and in mice with angiotensin-II induced cardiac hypertrophy. Overexpression of FPPS induced cardiac hypertrophy and fibrosis in mice, accompanied by an increase in the synthesis of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). In the present study, we investigated the mechanisms of reversing cardiovascular remodeling in SHR by inhibiting FPPS. Methods and Results: Six-week-old rats were given vehicle or an FPPS inhibitor (alendronate, 100 ug/kg/d) daily for twelve weeks by osmotic mini-pump. The results demonstrated that FPPS inhibition attenuated cardiac hypertrophy and fibrosis in SHR as shown by the heart weight to body weight ratio, echocardiographic parameters, and histological examination. In addition, FPPS inhibition attenuated aortic remodeling as shown by reduced media thickness, media cross-sectional area and collagen of the aorta as well as SBP, DBP, MBP. Furthermore, 12 weeks of alendronate treatment significantly decreased FPP and GGPP levels, RhoA activation and geranylgeranylation in the heart and aorta, all of which were significantly upregulated in SHR compared with normotensive Wistar-Kyoto rats. Conclusion: Taken together, these results indicate that chronic treatment with alendronate decreases the development of cardiac and aortic remodeling, by a pathway which involves inhibition of the geranylgeranylation and activation of RhoA.

Inhibition of NF-κB induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats

2005 ◽  
Vol 289 (1) ◽  
pp. H20-H29 ◽  
Author(s):  
Sudhiranjan Gupta ◽  
David Young ◽  
Subha Sen
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Cardiac Mass ◽  
Heart Weight ◽  
Pyrrolidine Dithiocarbamate ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Iκb Kinase

The transcription factor nuclear factor (NF)-κB plays a leading role in cardiac hypertrophy associated with heart failure, but whether it is involved in cardiac mass reduction is not known. We evaluated whether inhibiting the NF-κB cascade with pyrrolidine dithiocarbamate (PDTC) in spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto rats (WKYs) affected hypertrophy. We measured NF-κB signaling components [NF-κB translocation, IκBα, p65, mRNA and protein levels, and IκB kinase-β (IKKβ) activity] at 12 and 36 wk in WKYs and SHRs and at 10 wk in PDTC-treated rats ( n = 9). NF-κB activation was also evaluated in rats treated for 10 wk with captopril or hydralazine alone or with either drug plus PDTC. All components were increased in SHRs compared with WKYs. After PDTC treatment, NF-κB activity was inhibited, and heart weight-to-body weight ratio in SHRs was significantly attenuated (3.52 ± 0.04 to 3.32 ± 0.05 mg/kg). Captopril treatment significantly reduced cardiac mass (3.5 vs. 3.05 mg/kg; n = 9) and inhibited NF-κB activity (169.71 ± 5.70 to 106.7 ± 12.44). Hydralazine had no effect on cardiac mass (3.5 vs. 3.42 mg/kg) or NF-κB activity (169.71 ± 5.70 to 155.52 ± 6.11). Hydralazine plus PDTC reduced blood pressure (191.16 ± 1.7 to 158.5 ± 2.36 mmHg) and inhibited NF-κB activity (169.71 ± 5.70 to 97.29 ± 3.65). Our data suggest that 1) cardiac hypertrophy in SHRs is partly due to NF-κB activation, 2) inhibition of NF-κB activity by PDTC parallels regression of hypertrophy, and 3) regression of hypertrophy is partly due to inhibition of NF-κB activity, independent of hypertension. The relationship between NF-κB activity and cardiac remodeling is causal, not coincidental.

Distensibility of the Left Atrial Wall in Spontaneously Hypertensive Rats Compared with That in Normotensive Wistar-Kyoto Rats

1980 ◽  
Vol 59 (s6) ◽  
pp. 361s-363s
Author(s):  
S.-E. Ricksten ◽  
T. Yao ◽  
B. Ljung ◽  
P. Thorean
Keyword(s):  
Left Atrial ◽  
Spontaneously Hypertensive Rats ◽  
Relative Length ◽  
Hypertensive Rats ◽  
Atrial Wall ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Left Atrial Wall ◽  
Wistar Kyoto

1. The cardiac mechanoreceptors, which in rats are mainly located in the left atrial wall, are reset in spontaneously hypertensive rats. The atrial pressure has to be almost twice as high in spontaneously hypertensive rats as in normotensive controls to produce similar receptor activations, as is apparent from previous studies. 2. The present study was performed to investigate whether this resetting is due to decreased distensibility of left atrial walls in the spontaneously hypertensive rats. 3. Static load-length relationships were investigated in vitro on left atrial strips, and pressure-volume relationships were studied on isolated left atria from spontaneously hypertensive and normotensive Wistar-Kyoto rats. 4. The force per cross-sectional area exerted during a relative length increase of 80% was significantly greater in spontaneously hypertensive rats. The dynamic but not the static distensibility was significantly lower in these animals. 5. The decreased dynamic distensibility of left atrial walls in spontaneously hypertensive rats can at least partly explain the resetting of atrial receptor function.

scholarly journals Proteomic identification of the proteins related to cigarette smoke-induced cardiac hypertrophy in spontaneously hypertensive rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuki Kitamura ◽  
Nathan Mise ◽  
Yurie Mori ◽  
Yuka Suzuki ◽  
Tomoki Ohashi ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cigarette Smoke ◽  
Spontaneously Hypertensive Rats ◽  
High Dose ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Difference Gel Electrophoresis ◽  
Wistar Kyoto ◽  
Shock Proteins

Abstract Smoking increases the risk of cardiovascular diseases. The present study was designed to determine the effects of 2-month exposure to cigarette smoke (CS) on proteins in the left ventricles of spontaneously hypertensive rats (SHR) and to identify the molecular targets associated with the pathogenesis/progression of CS-induced cardiac hypertrophy. SHR and Wistar Kyoto rats (WKY) were exposed to CS at low (2 puffs/min for 40 min) or high dose (2 puffs/min for 120 min), 5 days a week for 2 months. Using the two-dimensional fluorescence difference gel electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression levels of proteins in the whole left ventricles induced by long-term smoking. High-dose CS mainly caused cardiac hypertrophy in SHR, but not WKY, but no change in blood pressure. Proteomic analysis identified 30 protein spots with significant alterations, with 14 up-regulated and 16 down-regulated proteins in the left ventricles of CS-exposed SHR, compared with control SHR. Among these proteins, two members of the heat shock proteins (HSP70 and HSP20) showed significant up-regulation in the left ventricles of CS high-dose SHR, and the results were confirmed by western blot analysis. Our findings suggested that HSPs play an important role in regulation of CS-induced cardiac hypertrophy.

Myocardial meta-[125I]iodobenzylguanidine uptake in awake genetically hypertensive rats at different ages: an autoradiographic study

1999 ◽  
Vol 77 (6) ◽  
pp. 398-406 ◽  
Author(s):  
Carole Schwebel ◽  
Andrée Durand ◽  
Diane Godin-Ribuot ◽  
Olivier Provendier ◽  
Pierre Demenge
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Autoradiographic Study ◽  
Mibg Uptake ◽  
Hypertensive Rats ◽  
Heterogeneous Distribution ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Arterial Blood ◽  
Wistar Kyoto

The purpose of this work was to evaluate changes in myocardial meta-[125I]iodobenzylguanidine ([125I]MIBG) uptake and distribution with age in awake spontaneously hypertensive rats (SHR) with respect to Wistar-Kyoto (WKY) rats. Rats were randomly divided into two groups, one for measuring myocardial [125I]MIBG uptake and distribution 4 h after its injection and the second for evaluating myocardial catecholamine concentrations. Mean arterial blood pressure, cardiac hypertrophy index (heart/body weight ratio), and heart rate were significantly higher with increasing age in SHR compared with matched WKY rats. Myocardial catecholamine concentrations and turnover did not differ between the two strains and were significantly decreased with increasing age. Myocardial [125I]MIBG uptake determined by gamma counting was similar in WKY rats and SHR and did not vary significantly with age when expressed as uptake density. However, in both strains of rats, [125I]MIBG uptake determined by autoradiography was significantly greater at the base of the heart than at the apex and midventricular levels, and the uptake values of young rats were significantly higher than those of older rats. In 21-week-old WKY rats and SHR, the highest [125I]MIBG uptake values were found in the right ventricle. Thus, quantitative autoradiography allowed detection of significant changes in myocardial [125I]MIBG uptake and showed its heterogeneous distribution in the rat heart.Key words: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats, myocardial meta-[125I]iodobenzylguanidine uptake, sympathetic drive.

scholarly journals Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S84-S90 ◽  
Author(s):  
Daniel Casellas ◽  
Abderraouf Herizi ◽  
Annie Artuso ◽  
Albert Mimran ◽  
Bernard Jover
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renal Injury ◽  
Spontaneously Hypertensive Rats ◽  
Candesartan Cilexetil ◽  
Vascular Lesions ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
Renal Protection ◽  
Spontaneously Hypertensive

Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against NG-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5—20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.

scholarly journals Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats

2001 ◽  
Vol 280 (2) ◽  
pp. H668-H673 ◽  
Author(s):  
Kohji Abe ◽  
Miwa Tokumura ◽  
Tetsuji Ito ◽  
Takashi Murai ◽  
Akira Takashima ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Heart Weight ◽  
Hypertensive Rats ◽  
Continuous Administration ◽  
Spontaneously Hypertensive ◽  
Heart Dysfunction ◽  
Hemodynamic Deterioration ◽  
Significant Difference ◽  
Permanent Occlusion ◽  
Wistar Kyoto

We investigated the possible contribution of inducible nitric oxide synthase (iNOS) to postischemic heart dysfunction and injuries in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP, 13–14 wk of age, had significantly higher systolic blood pressure and greater heart weight than age-matched Wistar-Kyoto rats (WKY). Permanent occlusion of the left anterior descending coronary artery (LAD) caused significant and long-lasting increases in the activity and mRNA expression of myocardial iNOS in SHRSP compared with WKY. However, there was no significant difference in the LAD occlusion-induced expression of interleukin-1β mRNA between SHRSP and WKY. Hemodynamic deterioration and myocardial fibrosis were also observed in SHRSP at 4 wk after LAD occlusion. Continuous administration of 2-amino-5,6-dihydro-6-methyl-4 H-1,2-thiazin (AMT) completely blocked the LAD occlusion-induced increase in the myocardial iNOS activity of SHRSP. Moreover, postischemic heart dysfunction and injuries were also significantly ameliorated by 2-amino-5,6-dihydro-6-methyl-4 H-1,2-thiazin (AMT). These results suggest that the increased activity of myocardial iNOS plays a pivotal role in the development of postischemic cardiac dysfunction and injuries in SHRSP with the hypertensive and hypertrophic heart.

scholarly journals Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fibrosis in Spontaneously Hypertensive Rats

2015 ◽  
Vol 36 (4) ◽  
pp. 1453-1466 ◽  
Author(s):  
Marcelo D.M. Cezar ◽  
Ricardo L. Damatto ◽  
Luana U. Pagan ◽  
Aline R.R. Lima ◽  
Paula F. Martinez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Spontaneously Hypertensive Rats ◽  
Type I Collagen ◽  
Myocardial Function ◽  
Type I ◽  
Hypertensive Rats ◽  
Collagen Concentration ◽  
Cross Sectional ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Background: We evaluated the role of the aldosterone blocker spironolactone in attenuating long-term pressure overload-induced cardiac remodeling and heart failure (HF) in spontaneously hypertensive rats (SHR). Methods and Results: Thirteen month-old male SHR were assigned to control (SHR-C, n=20) or spironolactone (SHR-SPR, 20 mg/kg/day, n=24) groups for six months. Normotensive Wistar-Kyoto rats (WKY, n=15) were used as controls. Systolic blood pressure was higher in SHR groups and unchanged by spironolactone. Right ventricular hypertrophy, which characterizes HF in SHR, was less frequent in SHR-SPR than SHR-C. Echocardiographic parameters did not differ between SHR groups. Myocardial function was improved in SHR-SPR compared to SHR-C [developed tension: WKY 4.85±0.68; SHR-C 5.22±1.64; SHR-SPR 6.80±1.49 g/mm2; -dT/dt: WKY 18.0 (16.0-19.0); SHR-C 20.8 (18.4-25.1); SHR-SPR 28.9 (24.2-34.6) g/mm2/s]. Cardiomyocyte cross-sectional area and total collagen concentration (WKY 1.06±0.34; SHR-C 1.85±0.63; SHR-SPR 1.28±0.39 µg/mg wet tissue) were greater in SHR-C than WKY and SHR-SPR. Type 3 collagen expression was lower in SHR-C than WKY and unchanged by spironolactone. Soluble collagen, type I collagen, and lysyl oxidase did not differ between groups. Conclusion: Early spironolactone treatment decreases heart failure development frequency by improving myocardial systolic and diastolic function and attenuating hypertrophy and fibrosis in spontaneously hypertensive rats.

scholarly journals Ribonucleic acid synthesis in the myocardium of spontaneously hypertensive rats. Quantification of transcribing ribonucleic acid polymerases

1980 ◽  
Vol 188 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Constantinos J. Limas
Keyword(s):  
Cardiac Hypertrophy ◽  
Ribonucleic Acid ◽  
Spontaneously Hypertensive Rats ◽  
Acid Synthesis ◽  
Rna Polymerases ◽  
Chain Elongation ◽  
Hypertensive Rats ◽  
Appreciable Change ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Cardiac hypertrophy accompanies the progressive rise in blood pressure in spontaneously hypertensive rats. The role of endogenous RNA polymerases in this process was examined in nuclei from isolated cardiac myocytes of 20-week-old spontaneously hypertensive rats and normotensive Wistar–Kyoto controls. Both template-engaged (involved in transcription) and free (loosely attached to endogenous template, transcribing only with exogenous templates) RNA polymerases were increased in spontaneously hypertensive rats. In addition, the ratio of RNA polymerases I/II was lower in the spontaneously hypertensive rats for both functional pools of the enzyme. Endogenous transcribing RNA polymerases were quantified by t.l.c. of RNA-hydrolysis products. Increased numbers of enzyme molecules were present in nuclei from spontaneously hypertensive rats, without appreciable change in the rate of polyribonucleotide-chain elongation. These results could not be explained by differences in the activities of contaminating phosphatases or ribonucleases, nor by changes in endogenous nucleoside pools or recoveries of labelled nucleosides. Enhanced myocardial RNA synthesis in the spontaneously hypertensive rats at the stage of established cardiac hypertrophy is associated with increased numbers of RNA polymerase molecules. This increase may, in turn, reflect altered chromatin structure, resulting in increased polymerase binding and/or chain initiation.

Cardiac and renal hyperplasia in newborn spontaneously hypertensive rats

1987 ◽  
Vol 72 (3) ◽  
pp. 271-275 ◽  
Author(s):  
Jaroslav Kunes ◽  
Stephen C. Pang ◽  
Marc Cantin ◽  
Jacques Genest ◽  
P. Hamet
Keyword(s):  
Body Weight ◽  
Dna Content ◽  
Spontaneously Hypertensive Rats ◽  
Weight Ratio ◽  
Total Body Weight ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Relative Dna Content ◽  
Wistar Kyoto ◽  
Total Body

1. Cardiac hyperplasia in newborn spontaneously hypertensive rats (SHR) has been noted by our group as well as by other investigators. The present study was designed to establish whether early (neonatal) hyperplasia is confined to the heart or is a generalized phenomenon in this hypertensive model. 2. The ventricles, kidney and liver of newborn SHR, Wistar and Wistar-Kyoto (WKY) rats were analysed for their protein and DNA content. 3. Total organ weight and the organ/body weight ratio of the heart and kidney but not of the liver were significantly greater in the SHR than in the control rats, irrespective of total body weight. 4. The higher relative DNA content (per 100 mg of tissue or 100 g body weight) indicated that hyperplasia rather than hypertrophy was responsible for the enlarged heart as well as the kidney of newborn SHR. 5. The cause of this selective cardiac and renal hyperplasia is not yet known: it may be due to putative ‘haemodynamic growth stimuli’, an intrinsic genetic abnormality of cells in the heart and kidney, circulating growth-promoting factors, or innervation.

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