Amelioration of Angiotensin Ii-Induced Cardiac Injury by Hmg-Coa Reductase Inhibition

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 683-683
Author(s):  
Ralf Dechend ◽  
Anette Fiebeler ◽  
Joon-Keun Park ◽  
Dominik N Muller ◽  
Jurgen Theuer ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Plasma Cholesterol ◽  
Cardiac Injury ◽  
Immunohistochemical Analysis ◽  
Ang Ii ◽  
Cholesterol Reduction ◽  
Mobility Shift ◽  
Hmg Coa Reductase ◽  
Coa Reductase

32 HMG-CoA reductase inhibitors have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury. We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from week 4 to 7 with cerivastatin (0.5 mg/kg/d by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and RT-PCR techniques. Compared to control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I and IV deposition. Total plasma cholesterol was not different between the groups. Immunohistochemical analysis showed increased expression of basic fibroblast growth factor (b-FGF), IL-6, and the NF-κB subunit p65 in the media of dTGR, which was markedly reduced by cerivastatin. b-FGF mRNA in the left ventricle was also significantly reduced. The transcription factors NF-κB and AP-1 were substantially less activated in the left ventricle. These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, and remodeling, independent of cholesterol reduction. They suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

scholarly journals AT1 receptor participates in the cardiac hypertrophy induced by resistance training in rats

2008 ◽  
Vol 295 (2) ◽  
pp. R381-R387 ◽  
Author(s):  
Valerio G. Barauna ◽  
Flávio C. Magalhaes ◽  
Jose E. Krieger ◽  
Edilamar M. Oliveira
Keyword(s):  
Resistance Training ◽  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Receptor Gene ◽  
Weight Ratio ◽  
High Salt ◽  
Receptor Expression ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet

Resistance training is accompanied by cardiac hypertrophy, but the role of the renin-angiotensin system (RAS) in this response is elusive. We evaluated this question in 36 male Wistar rats divided into six groups: control ( n = 6); trained ( n = 6); control + losartan (10 mg·kg−1·day−1, n = 6); trained + losartan ( n = 6); control + high-salt diet (1%, n = 6); and trained + high-salt diet (1%, n = 6). High salt was used to inhibit the systemic RAS and losartan to block the AT1 receptor. The exercise protocol consisted of: 4 × 12 bouts, 5×/wk during 8 wk, with 65–75% of one repetition maximum. Left ventricle weight-to-body weight ratio increased only in trained and trained + high-salt diet groups (8.5% and 10.6%, P < 0.05) compared with control. Also, none of the pathological cardiac hypertrophy markers, atrial natriuretic peptide, and αMHC (α-myosin heavy chain)-to-βMHC ratio, were changed. ACE activity was analyzed by fluorometric assay (systemic and cardiac) and plasma renin activity (PRA) by RIA and remained unchanged upon resistance training, whereas PRA decreased significantly with the high-salt diet. Interestingly, using Western blot analysis and RT-PRC, no changes were observed in cardiac AT2 receptor levels, whereas the AT1 receptor gene (56%, P < 0.05) and protein (31%, P < 0.05) expressions were upregulated in the trained group. Also, cardiac ANG II concentration evaluated by ELISA remained unchanged (23.27 ± 2.4 vs. 22.01 ± 0.8 pg/mg, P > 0.05). Administration of a subhypotensive dose of losartan prevented left ventricle hypertrophy in response to the resistance training. Altogether, we provide evidence that resistance training-induced cardiac hypertrophy is accompanied by induction of AT1 receptor expression with no changes in cardiac ANG II, which suggests a local activation of the RAS consistent with the hypertrophic response.

Apple phlorizin reduce plasma cholesterol by down-regulating hepatic HMG-CoA reductase and enhancing the excretion of fecal sterols

2019 ◽  
Vol 62 ◽  
pp. 103548
Author(s):  
Hao Wang ◽  
Zhen-ou Sun ◽  
Rizwan ur-Rehman ◽  
Sania Riaz ◽  
Ting-Ting Shen ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Hmg Coa Reductase ◽  
Fecal Sterols ◽  
Coa Reductase ◽  
Reduce Plasma Cholesterol

scholarly journals Effect of selenium deficiency on hepatic lipid and lipoprotein metabolism in the rat

1997 ◽  
Vol 78 (3) ◽  
pp. 493-500 ◽  
Author(s):  
F. Nassir ◽  
C. Moundras ◽  
D. Bayle ◽  
C. Sérougne ◽  
E. Gueux ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Liver Microsomes ◽  
Ldl Receptor ◽  
Selenium Deficiency ◽  
Cholesterol Concentration ◽  
Deficient Diet ◽  
Hmg Coa Reductase ◽  
Hepatic Lipid ◽  
Se Deficiency ◽  
Coa Reductase

Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.Selenium: Cholesterol: Triacylglycerol: HMG-CoA reductase

scholarly journals Angiotensin II receptor blocker LCZ696 attenuates cardiac remodeling through the inhibition of the ERK signaling pathway in mice with pregnancy-associated cardiomyopathy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yi Wang ◽  
Zhiheng Guo ◽  
Yongmei Gao ◽  
Ping Liang ◽  
Yanhong Shan ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Cardiac Injury ◽  
Erk Signaling ◽  
Ang Ii ◽  
Total Survival

Abstract Pregnancy-associated cardiomyopathy (PAH) represents a pregnancy-associated myocardial disease that is characterized by the progression of heart failure due to marked left ventricular systolic dysfunction. Compelling evidence has highlighted the potential of angiotensin (Ang) receptor inhibitors as therapeutic targets in PAH treatment. The present study aims to elucidate the molecular mechanisms underlying Ang II receptor inhibitor LCZ696 treatment in PAH. Initially, a PAH mouse model was induced, followed by intraperitoneal injection of LCZ696. Subsequently, cardiomyocytes and fibroblasts were isolated, cultured, and treated with Ang II and LCZ696, followed by detection of the total survival rate, cardiac injury, cardiac fibrosis and apoptosis. Moreover, in order to quantify the cardiac hypertrophy and fibrosis degree of cardiac fibroblasts, the expression levels of markers of cardiac hypertrophy (ANP, βMHC and TIMP2) and markers of fibrosis (collagen I, collagen III and TGF-β) were evaluated. Furthermore, the potential effect of LCZ696 on the extracellular signal-regulated kinase (ERK) signaling pathway was examined. The acquired findings revealed that LCZ696 increased the total survival rate of PAH mice, but decreased cardiac injury, cardiac fibrosis, and apoptosis in vitro. LCZ696 attenuated cardiac injury induced by Ang II through the inhibition the expression of markers of cardiac hypertrophy, fibrosis and apoptosis by inhibiting ERK phosphorylation in vivo and in vitro. Altogether, LCZ676 could potentially alleviate cardiac remodeling in mice with PAH via blockade of the ERK signaling pathway activation. Our findings suggest that LCZ696 could be a potential target for PAH therapy.

Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle

2002 ◽  
Vol 282 (5) ◽  
pp. R1389-R1394 ◽  
Author(s):  
Lutz Moser ◽  
Jörg Faulhaber ◽  
Rudolf J. Wiesner ◽  
Heimo Ehmke
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Adult Rats ◽  
Primary Stimulus

Locally released endothelin (ET)-1 has been recently identified as an important mediator of cardiac hypertrophy. It is still unclear, however, which primary stimulus specifically activates ET-dependent signaling pathways. We therefore examined in adult rats ( n = 51) the effects of a selective ETA receptor antagonist in experimental models of cardiac hypertrophy, in which myocardial growth is predominantly initiated by a single primary stimulus. Rats were exposed to mechanical overload (ascending aortic stenosis), increased levels of circulating ANG II (ANG II infusion combined with hydralazine), or adrenergic stimulation (infusion of norepinephrine in a subpressor dose) for 7 days. All experimental treatments significantly increased left ventricular weight/body weight ratios compared with untreated rats, whereas systolic left ventricular peak pressure was increased only after ascending aortic stenosis. ETA receptor blockade exclusively reduced norepinephrine-induced cardiac hypertrophy and atrial natriuretic peptide gene expression. Blood pressure levels and heart rates remained unaffected during ETA receptor blockade in all experimental groups. These data indicate that in rat left ventricle, the ET-dependent signaling pathway leading to early development of cardiac hypertrophy and fetal gene expression is primarily activated by norepinephrine.

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