Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure

Mulder, Paul; Richard, Vincent; Bouchart, F; Dérumeaux, Geneviève; Münter, Klaus; Thuillez, Christian

doi:10.1016/s0008-6363(98)00159-x

Cited by 72 publications

(37 citation statements)

References 45 publications

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“…As already reported with selective ET A , mixed ET A -ET B receptor blockers, 8,23,24 and ACE inhibitors, 22,25,26 LU 135252 and trandolapril decrease arterial blood pressure, improve cardiac hemodynamics, limit left ventricular remodeling, and increase both fractional shortening and posterior wall thickening. This, together with the decrease in cardiac preload and afterload, results in an increased stroke volume and cardiac output and prevents the deterioration of global LV function, without affecting LV dP/dt max .…”

Section: Discussionsupporting

confidence: 66%

“…All treatments were provided by Knoll AG (Ludwigshafen, Germany) and given as food admix. Treatments were started 7 days after ligation, in agreement with previous studies, 8,9,11,17,18 to avoid interference with the healing process or the early distention of the infarct zone. Rats were weighed every week and their food intake was measured to allow adjustment of the drug concentrations in the chow.…”

Section: Treatments and Study Designmentioning

confidence: 87%

“…In our study, LU 135252 is used at a dose that selectively blocks ET A receptors, because the dose of 30 mg/kg per day blocks the ET Amediated vasoconstrictor response without modifying the ET B -mediated dilator response. 8 Finally, the duration of the treatment period is extremely important when studying survival. For example, the calcium channel antagonist amlodipine improves survival during the first 6 months, whereas no improvement of survival is observed after 9 months of treatment.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure

et al. 2002

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Background-In patients with congestive heart failure (CHF) receiving ACE inhibitors, acute administration of selective endothelin (ET) antagonists additionally improves systemic and cardiac hemodynamics. We investigated, in a rat model of CHF, whether such acute synergistic effects are sustained and accompanied, in the long term, by an additional limitation of left ventricular remodeling or an increase in survival. Methods and Results-Rats were subjected to coronary artery ligation and treated for 3 or 9 months with vehicle or with the ACE inhibitor trandolapril (Tr) (0.3 mg/kg Ϫ1 per day Ϫ1 ), the ET A antagonist LU 135252 (LU, 30 mg/kg Ϫ1 per day Ϫ1 ), or their combination starting 7 days after ligation. After 3 months, the combination decreased LV systolic-and end-diastolic pressures (Ϫ32% and Ϫ80%, respectively) more markedly than Tr (Ϫ21% and Ϫ61%, respectively) or LU alone (Ϫ14% and Ϫ48%, respectively). Echocardiographic studies revealed that all treatments limited LV dilatation and increased LV fractional shortening and cardiac index. All treatments equally reduced left ventricular collagen density, whereas only Tr or the combination reduced LV weight. Finally, although LU did not modify long-term survival, Tr and the combination of Tr with LU induced a similar improvement of survival. Conclusions-In this rat model, long-term combined administration of an ET A antagonist and an ACE inhibitor induces additional effects in terms of systemic and cardiac hemodynamics; however, this is not associated with an additional increase in long-term survival.

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Section: Discussionsupporting

confidence: 66%

Section: Treatments and Study Designmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure

et al. 2002

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“…Short-and long-axis images were acquired using a digital ultrasound system (Sonosite 180Plus, 21919 30th Drive SE, Bothell, WA, USA) with a 7.5 MHz sector-array probe. A 7.5 MHz probe has been used effectively in several studies for echocardiographic analysis in rats (16)(17)(18). Sonosite is a fully digitalised system of the most recent generation with excellent image quality and during the analysis the image was presented in a 17 00 screen to increase resolution.…”

Section: Echocardiographymentioning

confidence: 99%

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

et al. 2007

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The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TRa1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T 3 and T 4 levels in plasma were not changed at 2 weeks but T 3 was significantly lower and T 4 remained unchanged at 13 weeks. A twofold increase in TRa1 expression was observed after 13 weeks in the non-infarcted area, P!0.05 versus sham operated, while TRa1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TRb1 expression was found in the non-infarcted area at 13 weeks, P!0.05, while no change in TRb1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TRa1 and 1.6-fold decrease in TRb1 expression versus untreated, P!0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TRa1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TRa1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TRb1 also contributes to fetal phenotypic changes. a1-adrenergic signalling is, at least in part, involved in this response. 156 415-424 European Journal of Endocrinology

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“…Although ECE inhibition, by phosphoramidon, and selective ET A -receptor antagonism, by BQ-123, impairs cardiac contractility in isolated animal hearts perfused at constant flow, 181 ET A -receptor antagonism by LU 135252 restores cardiac output dose-dependently, decreases BP and heart rate, and limits left ventricular remodelling in rats with coronary ligation and developing heart failure. 123 In dogs with moderate CHF induced by intracoronary microembolisations, long-term therapy with the ET A/B -receptor blocker, bosentan, prevents the progression of left ventricular dysfunction and attenuates left ventricular remodelling. 118 However, mixed ET A/Breceptor antagonism, by TAK-044, did not alter haemodynamics or vascular remodelling in rabbits with sustained volume overload.…”

mentioning

confidence: 99%

Role of endothelin in cardiovascular disease

Agapitov

Haynes

2002

J Renin Angiotensin Aldosterone Syst

154

119

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Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system.

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Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure

Cited by 72 publications

References 45 publications

Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure

Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure

Time-dependent changes in the expression of thyroid hormone receptor α1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling

Role of endothelin in cardiovascular disease

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