Carvedilol prevents severe hypertensive cardiomyopathy and remodeling

Barone, Frank C.; Campbell, Wallace G.; Nelson, Allen H.; Feuerstein, Giora

doi:10.1097/00004872-199816060-00019

Cited by 39 publications

(42 citation statements)

References 53 publications

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“…32,33) The present findings indicate the prevention of myocardial fibrosis and degeneration based on the extent of pathological fibrosis and the extent of enhancement on MRI, and that carvedilol also reduced the mortality rate. This suggests that the actions of carvedilol as a β-blocker and an antioxidant, in addition to its β-blocking effect, were useful for preventing histological damage and fibrosis.…”

Section: Mri and Pathological Findingssupporting

confidence: 62%

<b>Carvedilol Prevents Myocardial Fibrosis in Hamsters</b>

et al. 2006

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SUMMARYThe objective of the present study was to determine if carvedilol protects against myocardial degeneration and fibrotic change, and reduces mortality in TO2 hamsters.Carvedilol was administered intraperitoneally to 8 week-old TO2 hamsters for 21 weeks at a dose of 11 mg/kg/day. There were 15 TO2 hamsters in the carvedilol group (group C) and 10 in the untreated group (group N). The control group consisted of 11 Fb hamsters (group F). The mortality rate was determined from the number of surviving hamsters after 29 weeks. Myocardial fibrosis was evaluated by MRI and histopathological examination. EF and LVDd were determined by echocardiography at 8 and 29 weeks, while the MRI score was calculated at 29 weeks.Mortality, histopathological fibrosis, and MRI score were all lower in group C than in group N. Carvedilol had a protective effect against myocardial fibrosis and decreased the mortality rate in TO2 hamsters. ( 2-4) Following this, β-blocker therapy became used for the treatment of chronic heart failure.We previously performed MRI studies in a hamster model of cardiomyopathy (Bio 14.6 hamster) and found abnormal sites of enhancement as well as delayed enhancement. We proposed that the enhanced areas were regions of myocardial degeneration and fibrosis. 5) Carvedilol is a β-blocker that also has α-blocking and antioxidant effects, which have been shown to reduce the mortality rate of patients with moderate to severe chronic cardiac failure by 35% to 65%, in addition to also lowering the rehospitalization rate. 3,4) In the present study, we assessed the effects of carvedilol [6][7][8] in another hamster model of dilated cardiomyopathy, the BioFrom the

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Section: Mri and Pathological Findingssupporting

confidence: 62%

<b>Carvedilol Prevents Myocardial Fibrosis in Hamsters</b>

et al. 2006

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“…These data suggest that chronic β-AR blockade can arrest the development of cardiomyopathy. The beneficial effects of β-AR blockade on cardiac fibrosis in response to hypertension (25,26), norepinephrine (27) and myocardial infarction (28) have also been shown. Even more interest-…”

Section: Discussionmentioning

confidence: 99%

β-Adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic Gsα mouse

et al. 1999

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“…21,22 Age-matched Wistar-Kyoto normotensive rats (nϭ4) were included in initial myocardial p38 MAPK activity comparisons.…”

Section: Time-course Studymentioning

confidence: 99%

“…By use of the leading-edge method, 22 systolic and diastolic thicknesses of the anterior and posterior walls and the left ventricular (LV) diameter were measured. Relative wall thickness (RWT) was calculated as RWTϭ(AWdϩPWd)/LVDd, where AWd is diastolic anterior wall thickness, PWd is diastolic posterior wall thickness, and EDV and EDS are LV end diastolic and LV end systolic volume, respectively.…”

Section: Echocardiography and Hemodynamic Monitoringmentioning

confidence: 99%

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Hypertensive End-Organ Damage and Premature Mortality Are p38 Mitogen-Activated Protein Kinase–Dependent in a Rat Model of Cardiac Hypertrophy and Dysfunction

Behr

Nerurkar²,

Nelson³

et al. 2001

Circulation

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109

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Background-Numerous pathological mediators of cardiac hypertrophy (eg, neurohormones, cytokines, and stretch) have been shown to activate p38 MAPK. The purpose of the present study was to examine p38 MAPK activation and the effects of its long-term inhibition in a model of hypertensive cardiac hypertrophy/dysfunction and end-organ damage. Methods and Results-In spontaneously hypertensive stroke-prone (SP) rats receiving a high-salt/high-fat diet (SFD), myocardial p38 MAPK was activated persistently during the development of cardiac hypertrophy and inactivated during decompensation. Long-term oral treatment of SFD-SP rats with a selective p38 MAPK inhibitor (SB239063) significantly enhanced survival over an 18-week period compared with the untreated group (100% versus 50%). Periodic echocardiographic analysis revealed a significant reduction in LV hypertrophy and dysfunction in the SB239063-treatment groups. Little or no difference in blood pressure was noted in the treatment or vehicle groups. Basal and stimulated (lipopolysaccharide) plasma tumor necrosis factor-␣ concentrations were reduced in the SB239063-treatment groups. In vitro vasoreactivity studies demonstrated a significant preservation of endothelium-dependent relaxation in animals treated with the p38 MAPK inhibitor without effects on contraction or NO-mediated vasorelaxation. Proteinuria and the incidence of stroke (53% versus 7%) were also reduced significantly in the SB239063-treated groups. Conclusions-These results demonstrate a crucial role for p38 MAPK in hypertensive cardiac hypertrophy and end-organ damage. Interrupting its function with a specific p38 MAPK inhibitor halts clinical deterioration. (Circulation. 2001;

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Carvedilol prevents severe hypertensive cardiomyopathy and remodeling

Abstract: These data indicate that carvedilol provides remarkable cardioprotection, by suppressing severe hypertension-induced cardiac remodeling and myopathies at doses that do not reduce systemic blood pressure.

Cited by 39 publications

References 53 publications

<b>Carvedilol Prevents Myocardial Fibrosis in Hamsters</b>

<b>Carvedilol Prevents Myocardial Fibrosis in Hamsters</b>

β-Adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic Gsα mouse

Hypertensive End-Organ Damage and Premature Mortality Are p38 Mitogen-Activated Protein Kinase–Dependent in a Rat Model of Cardiac Hypertrophy and Dysfunction

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