Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously hypertensive rats

Burla, A; Neves, Mário Fritsch; Oigman, Wille; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1016/j.ijcard.2006.01.007

Cited by 9 publications

(7 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In SHRs, LV diastolic dysfunction or the upregulation of MR signals was induced by long-term (6 to 12 weeks) salt loading. [11][12][13]34 These previous findings are compatible with the present ones in that short-term (4 weeks) salt loading was not sufficient to induce LV diastolic dysfunction in SHRs. However, shortterm salt loading caused diastolic dysfunction associated with ROS overproduction and MR promotion in SHR/cps.…”

Section: Discussionsupporting

confidence: 92%

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

et al. 2008

View full text Add to dashboard Cite

Abstract-Metabolic syndrome is a highly predisposing condition for cardiovascular disease and could be a cause of excess salt-induced organ damage. Recently, several investigators have demonstrated that salt loading causes left ventricular diastolic dysfunction associated with increased oxidative stress and mineralocorticoid receptor activation. We, therefore, investigated whether excess salt induces cardiac diastolic dysfunction in metabolic syndrome via increased oxidative stress and upregulation of mineralocorticoid receptor signals. Thirteen-week-old spontaneously hypertensive rats and SHR/NDmcr-cps, the genetic model of metabolic syndrome, were fed a normal salt (0.5% NaCl) or high-salt (8% NaCl) diet for 4 weeks. In SHR/NDmcr-cps, salt loading induced severe hypertension, abnormal left ventricular relaxation, and perivascular fibrosis. Salt-loaded SHR/NDmcr-cps also exhibited overproduction of reactive oxygen species and upregulation of mineralocorticoid receptor-dependent gene expression, such as Na ϩ /H ϩ exchanger-1 and serumand glucocorticoid-inducible kinase-1 in the cardiac tissue. However, in spontaneously hypertensive rats, salt loading did not cause these cardiac abnormalities despite a similar increase in blood pressure. An antioxidant, tempol, prevented salt-induced diastolic dysfunction, perivascular fibrosis, and upregulation of mineralocorticoid receptor signals in SHR/NDmcr-cps. Moreover, a selective mineralocorticoid receptor antagonist, eplerenone, prevented not only diastolic dysfunction but also overproduction of reactive oxygen species in salt-loaded SHR/NDmcr-cps. These results suggest that metabolic syndrome is a predisposed condition for salt-induced left ventricular diastolic dysfunction, possibly via increased oxidative stress and enhanced mineralocorticoid receptor signals. which eventually leads to diastolic heart failure with a poor prognosis. 5,6 However, LV diastolic dysfunction has not always been seen in a MetS animal model. For example, in obesity-prone Sprague-Dawley rats, a moderate fat diet induced metabolic abnormalities but did not cause LV diastolic dysfunction. 7 This discrepancy indicates a possibility that some exogenous factors deteriorate cardiac function in MetS. In patients with MetS, high salt intake increased blood pressure (BP) greater than in those without MetS. 8 In an MetS rat model, evident renal injury was induced by salt loading. 9 These findings suggest that the MetS model is highly susceptible to salt-induced organ damage. Salt loading induced LV hypertrophy or LV diastolic dysfunction in several hypertension models. 10 -14 Therefore, it is speculated that LV diastolic impairment could be accelerated with excess salt in an MetS model.Reactive oxygen species (ROS) are important elements causing cardiac functional damage. 10,15,16 MetS should be associated with an increase in oxidative stress, 17-19 possibly through enhanced ROS-inducible adipocytokines. 20 -22 Also, salt loading increased oxidative stress in several salt-sensitive hypertension models...

show abstract

Section: Discussionsupporting

confidence: 92%

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In SHR, the aldosterone blockade was evaluated during the cardiac remodeling process but not during heart failure development. In young [45,56,57,58,59] and mature [20,46] SHR, treatment with aldosterone blockers have resulted in improved or unchanged LV hypertrophy and myocardial fibrosis. The conflicting results after aldosterone blockers treatment suggest that their role in the remodeling process and heart failure development are not completely understood but are probably influenced by treatment period and experimental cardiac injury model.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Cezar

Damatto

Martinez

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR). Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer). Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004). Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg). Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

show abstract

“…Hypertension has indeed been shown to be a known risk factor for cardiac remodeling in non-diabetics, leading to hypertrophy and later cardiomyocyte loss and heart failure. Previous studies have shown that 6 weeks of hypertension is sufficient to induce early cardiac remodeling (Burla et al 2007). Our present findings indicate that 6 weeks of saltloading per se (without diabetes) and the rise in BP over 4 weeks increased the HW/BW ratio in group CS (Fig.…”

Section: Discussionmentioning

confidence: 99%

Early blood pressure-independent cardiac changes in diabetic rats

Landau¹,

Chayat

Zucker³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

Cardiac remodeling is a key event in both diabetic and hypertensive heart diseases. In the present study, we investigated early myocardial changes in an animal model, the male Sabra rat model (SBH/y) of salt-induced hypertension-rendered diabetic with streptozotocin. Control non-diabetic (C), diabetic (D), and D or C rats made hypertensive by salt loading (DS or CS) were studied after 6 weeks. M-mode echocardiography revealed that left ventricular internal dimension during diastole and systole were significantly increased in D and DS, but not in C or CS. Concurrently, we found in D and DS an increase in cardiac b-myosin heavy chain, atrial natriuretic peptide, skeletal a-actin mRNA, type III collagen, and transforming growth factor-b.Myocardial angiotensin-converting enzyme (ACE) mRNA levels were increased while ACE2 mRNA levels were decreased in both D and DS groups. Cardiac angiotensin-1 (AT1) receptor protein levels were unchanged but the levels of phosphorylated (p) ERK and Jun-NH 2 -protein kinase (JNK) were increased in D and DS. In conclusion, we detected early cardiac changes in diabetic rats that were unrelated to hypertension. The increase in ACE, the decrease in ACE2, and the increase in cardiac pERK and pJNK suggest an increase in free angiotensin II and AT1R signaling in the diabetic myocardium as a possible mechanism contributing to cardiac remodeling in diabetes.

show abstract

Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously hypertensive rats

Cited by 9 publications

References 43 publications

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Early blood pressure-independent cardiac changes in diabetic rats

Contact Info

Product

Resources

About