Increased endothelin-1 production in patients with chronic heart failure

Parker, John D.; Thiessen, Jake J.

doi:10.1152/ajpheart.00239.2001

Cited by 33 publications

(18 citation statements)

References 33 publications

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“…Increased ET-1 production and decreased endotheliumdependent vasodilation are key features of endothelial dysfunction in HF [6,7,18]. ET-1 increases systemic and pulmonary vascular resistance and contributes to myocardial ischaemia in HF [7,18].…”

Section: Discussionmentioning

confidence: 99%

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The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

et al. 2004

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Reduced endothelium-dependent vasodilator responses with increased synthesis of ET-1 (endothelin-1) are characteristics of endothelial dysfunction in heart failure and are predictive of mortality. Identification of treatments that correct these abnormalities may have particular benefit for patients who become refractory to current regimens. Hawthorn preparations have a long history in the treatment of heart failure. Therefore we tested their inhibitory effects on ET-1 synthesis by cultured endothelial cells. These actions were compared with that of GSE (grape seed extract), as the vasoactive components of both these herbal remedies are mainly oligomeric flavan-3-ols called procyanidins. This showed extracts of hawthorn and grape seed were equipotent as inhibitors of ET-1 synthesis. GSE also produced a potent endothelium-dependent vasodilator response on preparations of isolated aorta. Suppression of ET-1 synthesis at the same time as induction of endothelium-dependent vasodilation is a similar response to that triggered by laminar shear stress. Based on these results and previous findings, we hypothesize that through their pharmacological properties procyanidins stimulate a pseudo laminar shear stress response in endothelial cells, which helps restore endothelial function and underlies the benefit from treatment with hawthorn extract in heart failure.

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Section: Discussionmentioning

confidence: 99%

“…ET-1 increases systemic and pulmonary vascular resistance and contributes to myocardial ischaemia in HF [7,18]. Plasma levels of ET-1 and big ET-1 can be predictive of mortality in HF [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

et al. 2004

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“…Circulating levels of ET-1 are elevated in patients with chronic heart failure (CHF) caused by a combination of increased production and reduced clearance of ET-1 (86). Furthermore, activation of the endothelin system contributes to peripheral vasoconstriction and impaired endothelial function in patients with CHF (87), and plasma ET-1 levels were shown to predict survival (88).…”

Section: Chronic Heart Failurementioning

confidence: 99%

Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease

Schneider

Boesen

Pollock

2007

Annu. Rev. Pharmacol. Toxicol.

261

247

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First identified as a powerful vasoconstrictor, endothelin has an extremely diverse set of actions that influence homeostatic mechanisms throughout the body. Two receptor subtypes, ET A and ET B , which usually have opposing actions, mediate the actions of endothelin. ET A receptors function to promote vasoconstriction, growth, and inflammation while ET B receptors produce vasodilation, increases in sodium excretion, and inhibit growth and inflammation. Potent and selective receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure and atherosclerosis. However, results are often contradictory and complicated because of the tissue-specific vasoconstrictor actions of ET B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo. Considerable questions remain regarding whether ET A selective or non-selective ET A /ET B receptor antagonists would be useful in a range of clinical settings. Keywordsreceptor localization; pulmonary hypertension; heart failure; chronic kidney disease Shortly after it was discovered that the vascular endothelium releases a peptide capable of profound vasoconstriction, a considerable amount of attention was paid to the potential actions of endothelin in the pathogenesis of cardiovascular disease. We have since learned a great deal about how this paracrine factor influences function in an extremely wide range of areas including neurotransmission, cell growth and epithelial transport, just to name a few. This myriad of activities has allowed the endothelin system to garner a tremendous amount of attention from the pharmaceutical industry with the development of numerous receptor specific and non-specific antagonists as well as efforts to identify drugs that inhibit endothelin synthesis. This work has led to new therapeutic approaches to pulmonary arterial hypertension and most likely other diseases in the not too distant future. In addition to this enormous drug discovery effort, it has also become clear that endothelin plays an important physiological role in maintaining blood pressure homeostasis, for example, by facilitating the excretion of a high salt diet. Because of the almost bewildering range of actions of the endothelin peptides, we limit this review to focus on the receptor-specific cardiovascular actions of endothelin. ENDOTHELIN PEPTIDESEndothelin-1, a 21-amino-acid long peptide first isolated from the supernatant of cultured endothelial cells, is perhaps the most potent vasoconstrictor substance known (1). The human Address for Correspondence: David M. Pollock, Ph.D., Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912-2500, +1-706-721-8517 office, +1-706-721-9799 fax, dpollock@mcg.edu. NIH Public Access Author ManuscriptAnnu Rev Pharmacol Toxicol. Author manuscript; available in PMC 2010 February 22. P...

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“…1,2 This has deleterious consequences on the severity of hypertension itself, because it produces peripheral vasoconstriction, as well as on the heart, because: (1) it favors activation of other potentially cardiotoxic neurohumoral systems (renin-angiotensin system, endothelin, etc) 3,4 ; (2) it increases myocardial oxygen consumption; and (3) it directly exerts toxic (pro-apoptotic, pro-necrotic) effects on the myocardium. [5][6][7] Accordingly, it is now firmly established that administration of ␤-adrenergic receptor blockers favorably affects hypertension and heart failure, 8 most likely via correction of the aforementioned pathophysiological alterations.…”

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Sympathectomy or Doxazosin, But Not Propranolol, Blunt Myocardial Interstitial Fibrosis in Pressure-Overload Hypertrophy

et al. 2005

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Abstract-The adaptive changes that develop in the pressure-overloaded left ventricular (LV) myocardium include cardiomyocyte hypertrophy and interstitial fibrosis. Although the former is known to depend to a sizeable extent on sympathetic (over)activity, little information exists whether the same applies to the latter, ie, whether excess catecholamine exposure contributes to the imbalance between collagen deposition by fibroblasts and degradation by matrix metalloproteases (MMPs), eventually leading to LV collagen accumulation. Sprague-Dawley rats were subjected to abdominal aortic banding (B) or sham operation (S) and treated with ␤-blockade (Bb, oral propranolol, 40 mg/kg per day), chemical sympathectomy (Sx, 6-hydroxydopamine, 150 mg/kg intraperitoneal twice per week) or vehicle (Vh). Ten weeks later, systolic blood pressure, LV weight, collagen abundance (computer-aided histology), zymographic matrix metalloproteinase (MMP)-2 activity and its specific tissue inhibitor concentration (TIMP-2) were measured. Both sympathectomy and ␤-blockade failed to attenuate the banding-induced blood pressure elevation but significantly attenuated the attendant LV hypertrophy. As expected, pressure-overload hypertrophy was associated with interstitial fibrosis (collagen: 4.37Ϯ1.23% BVh versus 1.23Ϯ0.44% SVh, PϽ0.05), which was abolished by sympathectomy (2.55Ϯ1.31%, Pϭnot significant versus SSx) but left unchanged by ␤-blockade (4.11Ϯ1.23%, PϽ0.05 versus both SBb and BSx). ␤-blockade, but not sympathectomy, was also associated with an increased TIMP-2/MMP-2 ratio (PϽ0.05), indicating reduced interstitial collagenolytic activity. In separate groups of banded and sham-operated rats, treatment with the ␣-receptor blocker doxazosin (10 mg/kg per day) displayed similar antifibrotic and biochemical effects as sympathectomy. Thus in the course of experimental pressure overload, the sympathetic nervous system plays a major pro-fibrotic role, which is mediated via ␣-adrenergic but not ␤-adrenergic receptors. Key Words: collagen Ⅲ extracellular matrix Ⅲ fibrosis Ⅲ heart failure Ⅲ hypertrophy Ⅲ sympathectomy T here is extensive evidence that sympathetic nerve overactivity consistently accompanies hypertension in its uncomplicated stage and even more so after the progressive development of left ventricular (LV) hypertrophy, dysfunction, and failure. 1,2 This has deleterious consequences on the severity of hypertension itself, because it produces peripheral vasoconstriction, as well as on the heart, because: (1) it favors activation of other potentially cardiotoxic neurohumoral systems (renin-angiotensin system, endothelin, etc) 3,4 ; (2) it increases myocardial oxygen consumption; and (3) it directly exerts toxic (pro-apoptotic, pro-necrotic) effects on the myocardium. 5-7 Accordingly, it is now firmly established that administration of ␤-adrenergic receptor blockers favorably affects hypertension and heart failure, 8 most likely via correction of the aforementioned pathophysiological alterations.However, although it is well documented ...

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Increased endothelin-1 production in patients with chronic heart failure

Cited by 33 publications

References 33 publications

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease

Sympathectomy or Doxazosin, But Not Propranolol, Blunt Myocardial Interstitial Fibrosis in Pressure-Overload Hypertrophy

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Increased endothelin-1 production in patients with chronic heart failure

Cited by 33 publications

References 33 publications

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction

Contrasting Actions of Endothelin ETAand ETBReceptors in Cardiovascular Disease

Sympathectomy or Doxazosin, But Not Propranolol, Blunt Myocardial Interstitial Fibrosis in Pressure-Overload Hypertrophy

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Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease