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)

Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and an independent risk factor for cardiovascular morbidity and mortality. The presence and severity of LVH is best determined by echocardiography and expressed as left ventricular mass index or left ventricular wall thickness. Pathological LVH, in response to pressure or volume load on the heart, is characterised by myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast activity and a significant increase in collagen fibres in the myocardium. Early diagnosis and treatment of hypertension has significantly decreased the incidence of LVH and subsequent heart failure in many countries, but the choice of antihypertensive therapy alters the rate of reversal of LVH and the subsequent development of heart failure. Angiotensin converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers produce the most rapid reversal of hypertrophy. Meta-analysis of these many small trials suggests an advantage of ACE inhibitors over other groups of antihypertensive agents.
 ...
PMID:Hypertrophy to failure. 780 8

Myocardial hypertrophy is an established risk factor for cardiovascular morbidity and mortality. Beyond quantitative and mechanical aspects hypertrophy is associated with alterations in cardiac gene expression, resulting in a more fetal-like myocyte phenotype with a fragile Ca++ homeostasis. Depressed expression of sarcoplasmatic reticulum ATPase is the hallmark of this overload phenotype. Conversely, the gene expression and the activity of sodium calcium exchanger is up-regulated in endstage heart failure. Both alterations contribute to prolonged cytosolic Ca++ transients, disturbed relaxation and, probably, to electrophysiologic instability. Angiotensin II is a growth promoting agent and several lines of circumferential evidence suggest that the local formation of angiotensin II might contribute to the trophic response and phenotype shift in cardiac overload. The cardiac gene expression of angiotensin converting enzyme and angiotensinogen is increased early after cardiac overload and in patients with severe heart failure. Chronic ACE inhibition suppresses plasma and tissue ACE activity, reduces LV hypertrophy and improves long-term survival. The hallmark of the peripheral adaptation in chronic heart failure is systemic vasoconstriction, associated with neurohumoral activation. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data suggest an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia in patients with chronic heart failure. Moreover, alterations of skeletal muscle emerge in chronic heart failure contributing to reduced exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heart failure: an update on pathophysiology. 786 17

Recent developments in the techniques of molecular biology and the availability of inhibitors of the renin-angiotensin system have provided new insight into renin-angiotensin research. The control mechanism of renin release and the metabolism of circulating renin have been well characterized on the molecular level. Angiotensin II has been shown to play an important role not only in the regulation of blood pressure but also in cell growth and hypertrophy. ACE inhibitors are effective for the treatments of hypertension and heart failure. Furthermore, recent studies suggest that ACE inhibitors may prevent atherosclerosis and glomerulosclerosis. Angiotensin II receptor antagonists have similar beneficial effects. These effects of ACE inhibitors and angiotensin II-receptor antagonists may be mediated by growth factors and the extracellular matrix.
 ...
PMID:[Pharmacology of the renin-angiotensin system]. 795 18

Coronary resistance arteriolar diameter importantly regulates myocardial blood flow, and is influenced by circulating neurohumoral agents. Angiotensin II (A-II) is a circulating polypeptide that is chronically elevated in heart failure and serves as a potent peripheral vasoconstrictor agent. However, its effects on isolated coronary resistance arterioles is relatively unknown. We compared the vasomotor effects of A-II on coronary epicardial and resistance arterioles in vitro from both the canine and porcine heart in order to determine the effects of A-II in different vascular beds and species. Epicardial rings were studied under isometric recording conditions, while resistance arterioles (50-150 microns) were studied in vitro using a video imaging system to record diameter. A-II, whether applied to passively distended or preconstricted porcine resistance arterioles, did not cause vasoconstriction when applied as a bolus or as cumulative doses. In preconstricted canine resistance arterioles, A-II elicited dose-dependent vasodilation (EC50 = 0.2 nM). In passively distended canine arterioles, high concentrations of A-II (0.1 microM) applied as a bolus elicited transient vasoconstriction in 28% of the vessels studied. In large epicardial rings, A-II was a weak vasoconstrictor, with greater potency in canine arteries compared to porcine arteries. In canine arteries, vasoconstriction to A-II was augmented after incubation with indomethacin. In contrast to the findings in canine arteries, the A-II vasoconstrictor response in porcine coronary arteries was decreased after incubation with indomethacin or removal of the endothelium. Thus, A-II elicits the release of a vasodilator prostanoid in epicardial canine coronary arteries and a vasoconstrictor prostanoid in porcine vessels which modulate the vasomotor action of A-II.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of angiotensin II on canine and porcine coronary epicardial and resistance arteries. 798 58

Congestive heart failure is often preceded by a latent or preclinical phase in which patients are relatively asymptomatic. During this period, there is neuroendocrine activation, left ventricular dysfunction, and remodeling of the heart. The extent to which these activities are interrelated is unclear, but it appears from experimental studies that myocardial damage is associated with chronic sympathetic nervous system activation, left ventricular hypertrophy, and a subsequent increase in left ventricular volume. The nondamaged myocardial tissue demonstrates enhanced messenger RNA for angiotensinogen and angiotensin converting enzyme activity. Angiotensin II along with other trophic signals may prime the cell for "growth." Alteration of left ventricular function may produce unusual loading conditions on the myocardium. Stretch of membrane-bound ion channels may impart mechanical signals that may be transduced and expressed as cellular hypertrophy. Interstitial collagenase may be activated, leading to disruption of the collagen-supporting network. Elongated cells (eccentric hypertrophy), cell slippage, and cell dropout may contribute to the dilatative process. The end product is cardiac dilatation, inefficient left ventricular performance, and congestive heart failure. We have observed that an increase in left ventricular mass is the initial morphological response to acute myocardial damage in a canine model. This occurs at 1 week and is followed by progressive activation of the sympathetic nervous system, left ventricular dilatation, and modest left ventricular dysfunction, a condition that mimics preclinical heart failure in patients. The remodeling process in the canine model, including the increase in mass and volume, may be blocked by angiotensin converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. 809 70

Angiotensin II (Ang II) raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Ang II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT1), and may be blocked by losartan, a specific blocker of AT1 receptors. In particular, studies employing losartan have shown that Ang II is an important contributor to BP regulation and plays a significant role in hypertension and in the pathophysiology of vascular damage during the course of hypertension. Ang II is also involved in the process of atherosclerosis and in remodelling and repair processes of the myocardium following myocardial infarction. Finally, increased Ang II is an important part of neurohumoral activation in heart failure. Exciting new discoveries concerned with polymorphisms of genes coding for angiotensin converting enzyme (ACE) and angiotensinogen suggest that Ang II may be genetically associated with increased risk for myocardial infarction, hypertension and left ventricular hypertrophy.
 ...
PMID:Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. 858 76

The influence of heart failure on the process of cell communication was investigated in cell pairs isolated from the ventricle of cardiomyopathic hamsters (11 months old) and the results compared with age-matched normal hamsters. The gap junctional conductance (gj) was measured with two voltage-clamp amplifiers. The results showed two major populations of cell pairs with respect to gj values: one with very low values (0.8 to 2.5 nS) and the other with higher values (7 to 35 nS). In normal hamsters, the most frequent gj values were in the range of 40 to 100 nS. Angiotensin II (Ang 11, 1 microg/mL) caused cell uncoupling in myopathic myocytes with low gj but reduced gj by 53 +/- 6.6 percent (+/- SE) in cell pairs with higher gj values (7 to 35 nS). The effect of Ang II on gj of myopathic cell pairs was suppressed by losartan (10(-7) mol/L). In cardiomyopathic cell pairs with low gj (0.8 to 2.5 nS), enalapril (1 microg/mL) caused an appreciable increase in gj (219 +/- 20.3 percent), whereas in cell pairs with higher gj (7 to 35 nS), the gj increment was smaller (80 +/- 10.8 percent) but still larger than that seen in controls (33 +/- 5.4 percent). Intracellular dialysis of Ang I (10(-8) mol/L) abolished cell communication in myopathic cell pairs with low gj (0.8 to 2.5 nS) and reduced gj by 66 +/- 1.7 percent in the other pairs (7 to 35 nS). The effect of Ang I on gj was greatly reduced by enalaprilat (10(-9) mol/L) added to the cytosol. Dialysis of Ang II (10(-8) mol/L) into the myopathic cell reduced gj by 48 +/- 4.2 percent, an effect abolished by losartan (10(-8) mol/L). The results indicate that the decline in gj seen in the ventricle of cardiomyopathic hamsters is in part due to activation of the cardiac renin-angiotensin system.
 ...
PMID:Renin-angiotensin system and cell communication in the failing heart. 864 34

The renin-angiotensin system regulates normal cardiovascular homeostasis and is activated in certain forms of hypertension and in heart failure. Angiotensin II has multiple physiological effects and we have shown recently that its growth-promoting effects on vascular smooth muscle require autocrine activation of the IGF I receptor. To study the effect of angiotensin II on circulating IGF I, we infused rats with 500 ng/kg/min angiotensin II for up to 14 d. Angiotensin II markedly reduced plasma IGF I levels (56 and 41% decrease at 1 and 2 wk, respectively) and IGF binding protein-3 levels, and increased IGF binding protein-2 levels, a pattern suggestive of dietary restriction. Compared with sham, angiotensin II-infused hypertensive rats lost 18-26% of body weight by 1 wk, and pair-feeding experiments indicated that 74% of this loss was attributable to a reduction in food intake. The vasodilator hydralazine and the AT1 receptor antagonist losartan had comparable effects to reverse angiotensin II-induced hypertension, but only losartan blocked the changes in body weight and in circulating IGF I and its binding proteins produced by angiotensin II. Moreover, in Dahl rats that were hypertensive in response to a high-salt diet, none of these changes occurred. Thus, angiotensin II produces weight loss through a pressor-independent mechanism that includes a marked anorexigenic effect and an additional (likely metabolic) effect. These findings have profound implications for understanding the pathophysiology of conditions, such as congestive heart failure, in which the renin-angiotensin system is activated.
 ...
PMID:Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism. 864 43

Heart failure is a severe, disabling disease that portends a short life expectancy. This grave prognosis may be explained by growth-promoting effects of angiotensin II implicated in heart failure that mediate a genetic response called programmed cell death. The effects of angiotensin II are inhibited by angiotensin-converting enzyme (ACE) inhibitors, which improve exercise performance and quality of life, attenuate disease progression, and modestly lengthen survival. Unfortunately, mortality remains exceedingly high and may be partly attributable to augmented production of angiotensin II from a non-ACE chymase pathway. Angiotensin II production may therefore increase despite treatment with ACE inhibitors. The angiotensin II receptor antagonists are a new class of nonpeptide-reversible inhibitors that may offer clinical promise in heart failure through blockade of angiotensin II actions, whether produced from ACE or non-ACE chymase pathways.
 ...
PMID:Angiotensin II receptor blockers: novel therapy for heart failure? 866 7

In untreated congestive heart failure, aldosterone plasma concentrations are elevated in proportion to the severity of the disease and are further increased by the use of diuretic treatment. Angiotensin II, plasma potassium concentration, and corticotropin are the major stimulators of aldosterone synthesis. During angiotensin converting enzyme (ACE) inhibition, the role of alternative major or minor regulatory mechanisms may become significant. This may explain why during continuous ACE inhibition, after an initial reduction, plasma aldosterone measurements may subsequently increase to pretherapeutic levels. In addition to causing sodium and water retention, aldosterone contributes to hypokalaemia and hypomagnesaemia, which may induce electrical instability and death of cardiac myocytes. Aldosterone is also one factor involved in cardiac hypertrophy and fibrosis, which, together with myocardial cell death, may underlie progressive adverse myocardial remodelling. Evidence for a direct vascular effect of aldosterone suggests that this hormone may contribute to generalized vasoconstriction. Elevated plasma aldosterone levels can also contribute to depression of baroreflex sensitivity, and they are associated with increased mortality in patients with severe heart failure. Experimental and clinical research should be further expanded to investigate the potential benefits of opposing the effects of aldosterone by use of specific antagonists or other potentially more potent pharmacological agents with favourable side-effect profiles.
 ...
PMID:Aldosterone and heart failure. 868 70


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