Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary dysfunctions identified in the presence of chronic heart failure are an important pathophysiologic abnormality that influences the prognosis of the disease. Because the endothelin pathway plays a significant role in the increased peripheral vascular tone associated with heart failure, we hypothesized that the endothelin pathway may be involved in the abnormal coronary vasomotion associated with this pathologic condition. Experiments were carried out in failing hearts (UM-X7.1 cardiomyopathic hamsters, aged 225-250 days) and normal hearts (Syrian LVG hamsters, also aged 225-250 days). Isolated hearts were perfused at constant flow and exposed to the blocker of the generation of endothelin-1 (ET-1), phosphoramidon (10 microM infusion), as well as to the selective ET(A)-receptor antagonist BQ 123 (10 microM infusion) and to a selective ET(B)-receptor antagonist BQ 788 (1 microM infusion). Coronary and cardiac effects of exogenous ET-1 (0.01-100 pmol) were also studied. Phosphoramidon, BQ 788, and BQ 123 did not altered coronary perfusion pressure either in normal or in failing hearts, whereas cardiac contractility was significantly impaired in the presence of phosphoramidon and BQ 123. Coronary sensitivity to exogenous ET-1 did not demonstrate a significant difference between normal and failing hearts [median effective concentration (EC50), 7 pmol in failing hearts vs. 12 pmol in normal hearts; p = NS]. In the presence of exogenous ET-1, cardiac contractility was significantly increased in both groups. In normal hearts, the exogenous ET-1-induced increase in coronary perfusion pressure was completely antagonized by BQ 123, whereas combined administration of BQ 788 and BQ 123 was necessary to induce complete inhibition in failing hearts. The positive inotropic effect elicited by exogenous ET-1 (EC50) was completely abolished in the presence of BQ 123, whereas BQ 788 had no significant effect. Results indicate that the endothelin pathway does not play a significant role in the altered coronary vasomotion observed in this model of chronic heart failure. On the contrary, the endothelin pathway appears to participate in the maintenance of myocardial contractility. According to these observations, administration of an inhibitor of ET-1 synthesis, as well as the use of an ET(A)-receptor antagonist, may be contraindicated in the presence of poor left ventricular function because the endothelin pathway contributes significantly to the maintenance of cardiac contractility.
 ...
PMID:Effects of phosphoramidon, BQ 788, and BQ 123 on coronary and cardiac dysfunctions of the failing hamster heart. 967 15

1. Endothelium-dependent vasodilatation via nitric oxide in response to muscarinic stimulation is decreased in chronic heart failure while basal release of nitric oxide may be increased. As production of the endothelium-derived vasoconstrictor endothelin-1 is increased in chronic heart failure, endothelin-1 may act in an autocrine manner to modulate these effects. 2. To test this, we determined whether prolonged endothelin infusion in normal subjects would reproduce the alterations in basal and stimulated nitric oxide release observed in patients with chronic heart failure. Basal nitric oxide production was determined by measurement of forearm blood flow using strain gauge venous occlusion plethysmography before and after brachial artery infusion of a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine). Stimulated nitric oxide production was determined by brachial artery infusion of acetylcholine. As metabolic vasodilatation is thought to be mediated in part via nitric oxide and is decreased in chronic heart failure, forearm blood flow during peak reactive hyperaemia was also measured. Studies were then repeated during brachial artery infusion of endothelin-1 and a non-specific vasoconstrictor, noradrenaline. 3. Neither basal nor stimulated nitric oxide production was altered by endothelin-1 and noradrenaline infusion. However, absolute forearm blood flow responses to peak reactive hyperaemia were decreased during infusion of endothelin-1 in comparison to noradrenaline. These data suggest that increased endothelin-1 may not contribute greatly to altered basal and stimulated nitric oxide production in patients with chronic heart failure but may contribute to impaired metabolic vasodilatation, by mechanisms presumably unrelated to altered nitric oxide production.
 ...
PMID:Effect of endothelin-1 on endothelium-derived vascular responsiveness in man. 968 Apr 96

Endothelin is a very potent vasoconstrictor peptide produced by the vascular endothelium. Several studies have shown that the endothelin system is activated in various cardiovascular conditions, including myocardial infarction, heart failure and pulmonary hypertension. The known actions of the endothelin-1 isoform suggest that it may be an important mediator in several of the pathophysiological manifestations of heart failure. Data on the potential value of endothelin antagonists in heart failure are reviewed.
 ...
PMID:Update on endothelin. 971 20

Circulating endothelin-1, a very strong peptide vasoconstrictor first discovered in 1988, is raised in cardiac failure. This increase contributes to the deleterious effects of cardiac failure. Although specific anti-endothelin drugs are under development in this condition, the effects of more commonly used drugs on circulating endothelin-1 levels are not well known. The aim of this study was to evaluate the effects of ACE inhibitor therapy on plasma endothelin-1 levels in cardiac failure. The plasma endothelin-1 levels were measured in 24 patients (stages III and IV of the NYHA classification), before and after treatment with angiotensin converting enzyme inhibitor (Captopril: test doses, then 75 mg/day). A control group of 10 paired patients was used to shake off the effects of bed rest and hospital salt-free diet. The initial endothelin-1 levels were high but equivalent in the control and study groups: 9.13 +/- 1.87 fmol/mL vs 8.98 +/- 1.92 fmol/mL. Plasma endothelin-1 decreased significantly in the study group 72 hours after beginning ACE inhibitor therapy (7.44 +/- 1.95, p < 0.02) but remained higher than normal (p < 0.01), whereas the values in the control group remained the same. This study demonstrates a decreases in plasma endothelin-1 levels 72 hours after onset of ACE inhibitor therapy in patients with stable severe cardiac failure. This results, already suggested by many experimental studies and certain ancillary clinical trials, could explain some of the beneficial effects of ACE inhibitors in this condition.
 ...
PMID:[Rapid decrease of serum endothelin-1 levels after treatment with ACE inhibitors in chronic cardiac failure]. 974 64

The endothelins are a family of endothelium-derived peptides that possess characteristically sustained vasoconstrictor properties. Endothelin-1 appears to be the predominant member of the family generated by vascular endothelial cells. In addition to its direct vascular effects, endothelin-1 has inotropic and mitogenic properties, influences homeostasis of salt and water, alters central and peripheral sympathetic activity and stimulates the renin-angiotensin-aldosterone system. Studies with endothelin receptor antagonists have indicated that endothelin-1 probably has complex opposing vascular effects mediated through vascular smooth muscle and endothelial ET(A) and ET(B)receptors. Endogenous generation of endothelin-1 appears to contribute to maintenance of basal vascular tone and blood pressure through activation of vascular smooth muscle ET(A)receptors. At the same time, endogenous endothelin-1 acts through endothelial ET(B) receptors to stimulate formation of nitric oxide tonically and to oppose vasoconstriction. In view of the multiple cardiovascular actions of endothelin-1, there has been much interest in its contribution to the pathophysiology of hypertension. Results of most studies suggest that generation of, or sensitivity to, endothelin-1 is no greater in hypertensive than it is in normotensive subjects. Nonetheless, the deleterious vascular effects of endogenous endothelin-1 may be accentuated by reduced generation of nitric oxide caused by hypertensive endothelial dysfunction. It also appears likely that endothelin participates in the adverse cardiac and vascular remodelling of hypertension, as well as in hypertensive renal damage. Irrespective of whether vascular endothelin activity is increased in hypertension, anti-endothelin agents do produce vasodilatation and lower blood pressure in hypertensive humans. There is more persuasive evidence for increased endothelin-1 activity in secondary forms of hypertension, including pre-eclampsia and renal hypertension. Endothelin-1 also appears to play an important role in pulmonary hypertension, both primary and secondary to diseases such as chronic heart failure. The hypotensive effects of endothelin converting enzyme inhibitors and endothelin receptor antagonists should be useful in the treatment of hypertension and related diseases. Development of such agents will increase knowledge of the physiological and pathological roles of the endothelins, and should generate drugs with novel benefits.
 ...
PMID:Endothelin as a regulator of cardiovascular function in health and disease. 979 9

Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.
 ...
PMID:[Transition of myocardial ischemia to heart failure]. 981 48

An activated renin-angiotensin system is a major risk factor for cardiovascular events. Angiotensin II acts on AT1 and AT2 receptors. Stimulation of AT1 receptors is associated with endothelial dysfunction, mainly as the consequence of an increased vascular production of superoxide radicals, vasoconstriction, platelet activation, enhanced release of plasminogen activator inhibitor-1, activation of immediate early genes c-fos and c-jun, myocyte hypertrophy, connective tissue formation, endothelin-1 synthesis, and activation of growth factors like PDGF and TGF-beta 1. Stimulation of AT2 receptors can mitigate or abolish the growth promoting effects of AT1 receptor stimulation. The contribution of these effects--single or in combination--on the progression of atherosclerotic lesions, the phenomenon of restenosis and the process of remodeling in heart failure is being progressively elucidated. With increasing knowledge about these relationships the inhibition of AT1 receptors appears as a main target in preventive and reparative strategies in cardiovascular diseases.
 ...
PMID:Angiotensin II and coronary artery disease, congestive heart failure, and sudden cardiac death. 983 71

1. There is an ever increasing volume of evidence implicating endothelin-1 and its isoforms in a range of disease processes. These include asthma, pulmonary and essential systemic hypertension, cardiac failure and uterine dysfunction. 2. However, it is also important to realize that the endothelins play an obligatory role in normal cellular proliferation, repair and tissue development. 3. The present brief review focuses on some of the physiological and pathophysiological mediator roles of the endothelins and provides a sketch of the receptor systems and some of the signal transduction pathways that are now known to operate following receptor activation. 4. Importantly, it is now clear that the endothelins, their receptors and synthesis and degradation pathways offer potentially important therapeutic targets.
 ...
PMID:Endothelins in health and disease: an overview. 1006 36

Since 1992, adrenalectomy for pheochromocytoma has been recognized as a safe and efficient technique when performed by a laparoscopic approach. Most of the cases of pheochromocytomas treated as such and published in the literature were not associated with malignant hypertension and acute heart failure. We report the case of a 23-year-old woman who presented with this clinical picture and show that laparoscopic adrenalectomy may be as safe and efficient as conventional adrenalectomy when performed in this situation. The intraoperative changes in the secretion of catecholamines, endothelin-1, angiotensin II, N- and C-terminus of atrial natriuretic factor prohormone were also analyzed. Noradrenaline release during tumor dissection was associated with a stimulation of atrial natriuretic factor.
 ...
PMID:Heart failure induced by pheochromocytoma: laparoscopic treatment and intraoperative changes of several new cardiovascular hormones. 1009 71

In this article, we review the basic pharmacological and biochemical features of endothelin and the pathophysiological roles of endothelin in cardiovascular diseases. Development of receptor antagonists has accelerated the pace of investigations into the pathophysiological roles of endogenous endothelin-1 in various diseases, e.g. chronic heart failure, renal diseases, hypertension, cerebral vasospasm, and pulmonary hypertension. In chronic heart failure, the expression of endothelin-1 and its receptors in cardiomyocytes is increased, and treatment with an endothelin receptor antagonist improves survival and cardiac function. Endothelin receptor antagonists also improve other cardiovascular diseases. These results suggest that the interference with endothelin pathway either by receptor blockade or by inhibition of endothelin converting enzyme may provide novel therapeutic drugs strategies for multiple disease states.
 ...
PMID:Pathophysiology of endothelin in the cardiovascular system. 1009 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>