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)

Calcium antagonists are useful for the management of patients with ischaemic heart disease, particularly when used prophylactically. At the cellular level, these drugs act primarily by limiting calcium ion (Ca++) entry through the voltage-sensitive Ca(++)-selective channels, an effect that contributes markedly to their 'energy sparing' properties. However, the long term use of these drugs has additional advantages, particularly with respect to their ability to slow Ca(++)-dependent processes involved in the formation of atherogenic lesions, partially antagonise the effects of the raised levels of circulating endothelin-1 encountered during ischaemia-induced heart failure and hypertension, and trap and immobilise oxyradicals. Prolonged episodes of ischaemia result in an irreversible loss of homeostasis with respect to Ca++. However, the increase in myocardial cytosolic Ca++ caused by relatively short periods of ischaemia is small, reversible, and markedly attenuated by the prophylactic use of calcium antagonists. In the isolated, perfused rat heart, verapamil pretreatment produces statistically significant inhibition of the increase in cytosolic Ca++ during 20-minute global ischaemia. This stereospecific effect is associated with a decrease in the rise in total tissue Ca++ during reperfusion and amelioration of the adenosine triphosphate depletion caused by ischaemia. In general, discussion relating to the molecular basis of the use of calcium antagonists in the management of patients with ischaemic heart disease needs to take into account the duration of the ischaemic event, the workload on the myocardium, the need for prophylactic therapy, and the presence of exacerbating factors such as atherosclerosis and tobacco smoking. The early rise in cytosolic Ca++, the source of which remains uncertain, appears to be an important focus for anti-ischaemic drug therapy.
 ...
PMID:The molecular basis for the use of calcium antagonists in ischaemic heart disease. 137 84

Heart failure is commonly associated with high plasma concentrations of endothelin-1, a powerful vasoconstrictor produced by endothelium. The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist, bosentan. 24 patients with chronic heart failure received randomly and double blind two intravenous infusions of either placebo or bosentan (100 mg followed after 60 min by 200 mg). Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period. Baseline endothelin-1 and big-endothelin-1 concentrations, which were above the normal range in all patients, correlated directly with the extent of pulmonary hypertension, with left and right heart filling pressures, and with pulmonary vascular resistance and inversely with cardiac index. Compared with placebo, bosentan reduced mean arterial pressure by 7.7% (95% CI 7.1-9.7), pulmonary artery pressure by 13.7% (10.5-16.9), right atrial pressure by 18.2% (12.0-24.4), and pulmonary artery wedged pressure by 8.6% (5.3-12.0); it increased cardiac index by 13.6% (9.1-18.2), decreased systemic vascular resistance by 16.5% (13.2-19.8), and decreased pulmonary vascular resistance by 33.2% (22.4-44.0). Heart rate did not change. Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged. These findings indicate that, in patients with chronic heart failure who have high circulatory endothelin-1 concentrations, this peptide contributes to maintenance of vascular tone. The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients.
 ...
PMID:Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure. 765 74

Mesenteric artery and cardiac ventricular endothelin receptors and endothelin-1-induced pressor responses were studied in normal rats and rats with chronic congestive heart failure induced by myocardial ischemia (4 weeks after coronary artery ligation). In mesenteric arteries of rats with chronic ischemic heart failure, endothelin receptor density was significantly decreased by 59%, whereas the dissociation constant was increased 2.8-fold, as compared with controls. There were, however, no changes in endothelin-receptor density or the dissociation constant in cardiac ventricular membrane preparations from rats with congestive heart failure as compared with controls. In pithed rats with congestive heart failure there was a reduced pressor response to a bolus injection of endothelin-1 (800 pmole/kg body weight), while the vasodilatory response was unaltered as compared with sham-operated controls. These results demonstrate that there is a decreased vascular endothelin-receptor function due to a down-regulated endothelin receptor. The in vivo data indicate that this is due to impaired endothelin A but not endothelin B receptor function. Thus, there is an impaired arterial but not cardiac ventricular endothelin receptor-mediated signalling system in the rat with chronic ischemic heart failure.
 ...
PMID:Decreased density of mesenteric arteries but not of myocardial endothelin receptors and function in rats with chronic ischemic heart failure. 769 54

Endothelin is a powerful vasoconstrictor that may be partly responsible for the increases in venous and arterial tone characteristic of heart failure. The release of endothelin from endothelial cells in culture is stimulated by angiotensin II. We investigated the relationship between plasma concentrations of immuno reactive endothelin-1 and angiotensin II in 25 patients with heart failure and eight with ischaemic heart disease but normal left ventricular function. Plasma concentrations of endothelin and angiotensin II were correlated (Spearman rank correlation coefficient of 0.72; P < 0.0001) in patients with heart disease. Plasma concentrations of angiotensin II and endothelin were higher in those patients with heart failure. Angiotensin II was infused over a 3 h period in eight healthy volunteers. Infusion of angiotensin II increased plasma concentrations of angiotensin II to levels greater than those usually found in patients with severe heart failure but induced only a modest rise in plasma concentrations of immunoreactive endothelin-1 (0.77 +/- 0.16 to 1.03 +/- 0.03 pmol.l-1, P < 0.02). Increased plasma concentrations of angiotensin II and endothelin-1 both appear to reflect the presence and severity of heart failure. Although a significant correlation exists between plasma concentrations of angiotensin II and endothelin in patients with heart failure, the relationship may not be causal.
 ...
PMID:Elevated plasma endothelin concentrations in heart failure; an effect of angiotensin II? 769 33

In conclusion, plasma levels of the endothelial-derived vasoconstrictor endothelin-1 (but not those of other neurohormonal vasoconstrictor factors), measured during exercise correlated closely with objective variables of exercise capacity in patients with heart failure. These findings suggest that endothelin-1 may contribute to exercise intolerance in patients with heart failure, perhaps by limiting the ability of the peripheral vasculature to dilate during exercise.
 ...
PMID:Role of endothelin in the exercise intolerance of chronic heart failure. 777 60

Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide which also has important growth promoting effects on other cellular elements of the vascular wall. Increased local expression and release of endothelin-1 may therefore contribute to abnormal vascular tone and structure in paracrine fashion. Evidence of increased pulmonary production of endothelin-1 by the lung in patients with primary pulmonary hypertension is reviewed, including increased release across the pulmonary circulation and increased vascular expression of the peptide and its mRNA. However, circulating endothelin-1 might also have a humoral action on distant vascular beds. Changes in plasma endothelin-1 in response to postural change and chronic heart failure support a role for this potent vasoconstrictor factor in the neurohumoral response to haemodynamic stress. Thus, like other vascular regulatory mechanisms, the endothelin system might play a dual role in the control of vascular function with both local tissue and circulatory components.
 ...
PMID:Endothelin in cardiopulmonary disease: factor paracrine vs neurohumoral. 790 41

Left ventricular function and neurohormonal status in patients with heart failure remaining symptomatic during therapy with angiotensin-converting enzyme inhibitors were assessed, and the effects of dopaminergic receptor stimulation in this setting were determined. Neurohormonal and left ventricular function (radionuclide angiography) data were obtained in 19 patients with symptomatic ischemic heart failure. Measurements were repeated after 4 to 6 weeks of therapy with the dopamine agonist ibopamine (100 mg, 3 times/day) or placebo administered in a double-blind, randomized, parallel group design. At baseline, despite therapy with enalapril, the angiotensin II levels (mean 39.4 pg/ml; p < 0.01 vs controls) were significantly increased, as were plasma norepinephrine (497 +/- 240 pg/ml; p < 0.01 vs controls), endothelin-1, atrial natriuretic peptide and arginine vasopressin. Moreover, in comparison with pretreatment values, left ventricular ejection fraction had decreased substantially (-9.1%) in patients with plasma norepinephrine > or = 600 pg/ml, but not in those with lower values of norepinephrine. With ibopamine, plasma norepinephrine decreased from 516 +/- 241 to 391 +/- 208 pg/ml (n = 8; p < 0.025 vs placebo), whereas it increased with placebo. In conclusion, the neurohormonal control provided by an angiotensin-converting enzyme inhibitor is reduced in a large subset of patients during prolonged therapy; ibopamine appears to be a potentially useful drug to improve neurohormonal control in this setting.
 ...
PMID:Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor. 790 64

1. Plasma endothelin-1 (ET-1) levels are increased in chronic heart failure (CHF). Because chronic immunologic activation occurs in CHF and mononuclear cells (MNC) are capable of ET-1 production, the possible contribution of circulating MNC to the increased plasma ET-1 levels in CHF patients was investigated. 2. Unseparated MNC (10(7)/mL) from eight CHF patients spontaneously produced ET-1 (1.54 +/- 0.37 pg/100 mL). After separation of MNC into monocytes (10(6)/mL) and lymphocytes (10(7)/mL) at ratios approximating those in the circulationg, ET-1 was spontaneously produced by CHF lymphocytes (0.81 +/- 0.26 pg/100 mL), and after macrophage colony stimulating factor (MCSF) stimulation by CHF monocytes (0.56 +/- 0.08 pg/100 mL). In contrast, there was neither spontaneous nor MCSF-induced production of ET-1 in six normal subjects. 3. It was concluded that heightened ET-1 production by MNC may contribute to increased plasma levels in CHF patients. Because unseparated MNC produced greater ET-1 than lymphocytes and monocytes separately, contact between these MNC subtypes may be necessary for maximal ET-1 production.
 ...
PMID:Spontaneous endothelin production by circulating mononuclear cells from patients with chronic heart failure but not from normal subjects. 792 97

Elevated levels of the vasocontrictor peptide endothelin-1 have been demonstrated in various pathological conditions that are characterized by sodium retention and/or renal vasoconstriction, such as heart failure, hepatorenal syndrome, renal failure and during administration of cyclosporin and radiocontrast. In the present study we studied in seven healthy subjects the renal and endocrine effects of systemic administration of endothelin-1 (0.5, 1.0 and 2.5 ng/kg/min). During endothelin-1 infusion plasma levels rose from 3.2 +/- 0.5 to respectively 5.0 +/- 0.8, 6.2 +/- 0.5 and 8.5 +/- 1.1 pmol/liter, values that can also be observed in physiological and pathological conditions. Infusion of low dosages of endothelin-1, that result in a twofold increase in plasma levels, decreased sodium excretion by 36%, without a significant effect on systemic and renal hemodynamics. Infusion of 2.5 ng/kg/min of endothelin-1 further enhanced sodium retention and, in addition, increased renal vascular resistance by 37%. Blood pressure did not change significantly. Pretreatment with the calcium channel blocker nifedipine caused renal vasodilation, which compensated for the renal vasocontriction by endothelin-1 and prevented sodium retention. Apparently, endothelin-1 participates in volume homeostasis in human, whereas pathophysiological concentrations can contribute to renal vasoconstriction and sodium retention. Calcium channel blockers may protect against these effects of endothelin-1.
 ...
PMID:Effects of endothelin-1 on renal function in humans: implications for physiology and pathophysiology. 796 49

The vasoactive peptide hormones, such as endothelin, renin-angiotensin, and endothelium-derived relaxing factor, have traditionally been viewed as an endocrine system. Recent data demonstrate that their genes and their products are expressed at many local tissue sites. The concept that multiple tissues synthesis peptides has changed out understanding of the physiology of peptide hormone, and this indicated that the autocrine and paracrine system may be important in the regulation of local tissue functions in addition to the circulation endocrine system. Patients with congestive heart failure had markedly higher circulating endothelin-1 level than normal subjects, associated with an activated renin-angiotensin system. Endothelium-dependent vasodilation is attenuated in patients with heart failure. This impaired local vasodilation may contribute to abnormalities in vasoconstriction that are characteristic of heart failure.
 ...
PMID:[Hormonal regulation in cardiac function--endocrine, paracrine, autocrine]. 833 83


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