Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: Results of the ELITE ventricular function substudy

Konstam, Marvin A.; Patten, Richard D.; Thomas, Ignatious; Ramahi, Tarik M.; Bresh, Kenneth La; Goldman, Steven; Lewis, William R.; Gradman, Alan H.; Self, K. Stanley; Bittner, Vera; Rand, William; Kinan, Debra; Smith, Jordan; Ford, Tim; Segal, Robert; Udelson, James E.

doi:10.1067/mhj.2000.105302

Cited by 87 publications

(50 citation statements)

References 34 publications

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“…These observations gain support from findings indicating that AT 1 receptor blockers, such as losartan, markedly attenuate the development of atherosclerosis and the remodeling of infarcted myocardium. 34,35 …”

Section: Ang II and Its Receptors And Expression Of Tgf-␤1 Receptorsmentioning

confidence: 99%

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Chen²,

Mehta³

2001

Hypertension

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Abstract-Transforming growth factor-␤1 and its subtype receptor endoglin are key components in angiogenesis. We explored the role of angiotensin (Ang) II in the expression of endoglin and the underlying intracellular signaling mechanism in human coronary artery endothelial cells. Incubation of cells with Ang II upregulated endoglin expression in a concentration-and time-dependent manner (maximal effect with 10 Ϫ6 mol/L Ang II at 24 hours). The Ang II type 1 receptor blocker losartan, but not the type 2 receptor blocker PD 123,319, completely blocked the effect of Ang II. In parallel experiments, the mitogen-activated protein kinase inhibitor PD 098,059 fully inhibited the effect of Ang II on the expression of endoglin. Incubation of endothelial cells with Ang II also increased the expression of transforming growth factor-␤1 and -␤2 receptors and simultaneously decreased the levels of transforming growth factor-␤1. These effects of Ang II were also attenuated by losartan. We propose that Ang II via its type 1 receptor activation modulates the expression of transforming growth factor-␤1 receptors in human coronary endothelial cells. The activation of mitogen-activated protein kinase plays an important role in this process. These observations provide a new clue regarding the regulatory effect of Ang II on vascular remodeling after injury. (Hypertension. 2001;38:1062-1067.)

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Section: Ang II and Its Receptors And Expression Of Tgf-␤1 Receptorsmentioning

confidence: 99%

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Chen²,

Mehta³

2001

Hypertension

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“…It has been verified that AngII exerts deleterious effects as a potent vasoconstrictor and growth-promotor by inducing myocyte hypertrophy, myocardial fibroblast proliferation and collagen synthesis, and its AT1 receptor appears to mediate most of the adverse effects of AngII. 19,20 So the AT1 receptor antagonist, losartan, not only attenuates the reactive cardiac hypertrophy by its favorable hemodynamic profile, but also directly inhibits myocyte hypertrophy, fibroblast proliferation and collagen synthesis through AT1 receptor blockade. 19,21 The present study has shown that the combination of carvedilol and losartan is no more effective in attenuating cardiac hypertrophy than either drug alone, but further studies are needed to verify this apparent result.…”

Section: Effect Of Carvedilol and Losartan Alone And In Combination Omentioning

confidence: 99%

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

Yang

Tang

Ruan

et al. 2003

Circ J

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t is well known that left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) plays a very important role in progressive left ventricular (LV) dysfunction and subsequent heart failure. It is characterized by infarct expansion, hypertrophy of the noninfarcted myocardium and alteration of LV geometry, and manifests as progressive LV dilatation. Experimental studies have shown that angiotensin II type I (AT1) receptor antagonists, such as losartan, is beneficial in attenuating post-infarction LVRM. 1-4 Carvedilol, a third-generationblocker, is a unique, multiaction drug with non-selectiveblockade, 1-blockade and antioxidant effects. Clinical studies have shown that carvedilol is beneficial in preventing LVRM in patients with ischemic heart failure. 5,6 Therefore, we hypothesized that carvedilol should be effective, Circulation Journal Vol.67, February 2003 and its combination with losartan should be superior, in preventing post-infarction LVRM. So, the purpose of this study was to compare the effects of carvedilol and losartan alone and in combination on LVRM after AMI in rats. Methods Experimental Rats and GroupsAMI as induced by ligating the left coronary artery in 133 female Sprague-Dawley (SD) rats (body weight: 200-250 g). At 24 h after the operation, the 100 surviving rats were randomized to 4 groups: (1) AMI controls (n=25), (2) carvedilol (1 mg·kg -1 ·d -1 , n=25), (3) losartan (3 mg·kg -1 ·d -1 , n=25), and (4) carvedilol (1 mg·kg -1 ·d -1 ) + losartan (3 mg · kg -1 · d -1 ) (combination, n=25) groups. Sham-operated rats (n=17) were randomly selected before the AMI operation. MethodsAMI was conducted by a method previously reported by Olivetti et al. 7 After anaesthesia with ketamine (30 mg/kg) and diazepam (5 mg/kg), and then a thoracotomy, the left coronary artery of each rat was ligated using a 6-0 prolene suture, which induced an anterior myocardial infarction. In It has been verified that losartan has beneficial effects on ventricular remodeling (VRM) after acute myocardial infarction (AMI), but the effects of carvedilol alone or in combination with losartan on this condition have not been defined. The present study used rats to compare the effects of carvedilol and losartan alone and in combination for preventing VRM after AMI. After ligation of the left coronary artery, 100 surviving female SpragueDawley rats were randomly assigned to 1 of 4 groups: (1) AMI control (n=25), (2) carvedilol (Car, 1 mg·kg -1 · day -1 ) (n=25), (3) losartan (Los, 3 mg·kg -1 ·day -1 ) (n=25), and (4) Car (1 mg·kg -1 ·day -1 ) + Los (3 mg·kg -1 · day -1 ) (n=25). A sham-operated group (n=17) was also randomly selected. Drugs were administered by gastric gavage for 4 weeks. After hemodynamic studies, the hearts were fixed and analyzed pathologically. Exclusive of the rats that had died or had an infarct size <35% or >55%, complete data were obtained for 65 rats, comprising AMI control (n=13), Car (n=12), Los (n=13), combination (n=14), and sham (n=13)

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“…É sugerido, portanto, acompanhamento periódico da função ventricular em todo paciente pós-IAM, incluindo aqueles que não apresentam anormalidades nas avaliações iniciais 348 ; b) os parâmetros funcionais mais indicados para a determinação da função ventricular pós-IAM são a fração de ejeção ventricular esquerda e os volumes ventriculares, obtidos de forma não-invasiva por meio de ecocardiografia bidimensional, ressonância nuclear magnética ou ventriculografia radioisotópica 349 ; c) a decisão sobre a suspensão do uso dos inibidores da enzima conversora da angiotensina deve ser bem pesada, uma vez que os efeitos benéficos desses fármacos sobre a função cardíaca podem ser rapidamente reduzidos após a suspensão da terapia [350][351][352] . Ao se optar pela suspensão temporária ou definitiva, esta deverá ser feita de forma gradativa (se possível), uma vez que a retirada abrupta pode levar à piora clínica 353 .…”

Section: Utilização Dos Inibidores Da Enzima Conversora Daunclassified

“…Pode-se tentar a reintrodução desse agente após algumas semanas ou a substituição por um bloqueador seletivo dos receptores tipo I (AT1) da angiotensina II (bloqueadores AT1) ou da associação hidralazina e nitratos nos casos em que houver disfunção ventricular 354 ; d) angioedema é raro, mas muito grave, em geral ocorrendo na primeira semana de terapia, freqüentemente poucas horas após a ingestão da primeira dose do inibidor da enzima conversora da angiotensina. O edema é de rápida evolução e localizado no nariz e/ou na orofaringe; e) outros efeitos adversos descritos com os inibidores da enzima conversora da angiotensina são "rash" cutâneo, tontura, hipercalemia, e redução ou perversão do apetite 304,305,[332][333][334][335][336][337][351][352][353][354][355][356][357][358] .…”

Section: Utilização Dos Inibidores Da Enzima Conversora Daunclassified

III Diretriz sobre tratamento do infarto agudo do miocárdio

Avezum¹,

Carvalho²,

Mansur³

et al. 2004

Arq. Bras. Cardiol.

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Classe I: evidência ou concordância geral de que o tratamento é benéfico, útil e eficaz.Classe II: evidência conflitante e/ou divergência de opinião quanto à utilidade e à eficácia do tratamento.Classe IIa: forças das evidências/opiniões em favor da utilidade e da eficácia.Classe IIb: forças das evidências/opiniões menos bem estabelecidas quanto à utilidade e à eficácia.Classe III: evidência ou concordância geral de que o tratamento não é útil/eficaz e em alguns casos pode ser prejudicial. Nível de evidência A: presença de múltiplos estudos clínicos randomizados.Nível de evidência B: presença de um único estudo clínico randomizado ou de estudos não-randomizados.Nível de evidência C: consenso de especialistas.O nível de evidência será apresentado apenas para os tratamentos do infarto do miocárdio, não se aplicando aos procedimentos diagnósticos. Todos os métodos complementares deverão ser realizados por profissionais experientes, segundo as recomendações específicas de cada especialidade.

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Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: Results of the ELITE ventricular function substudy

Cited by 87 publications

References 34 publications

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Comparative Effects of Carvedilol and Losartan Alone and in Combination for Preventing Left Ventricular Remodeling After Acute Myocardial Infarction In Rats

III Diretriz sobre tratamento do infarto agudo do miocárdio

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