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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Heart failure: an update on pathophysiology. 786 17

Angiotensin converting enzyme inhibitors (ACEIs) are a cornerstone of treatment of hypertension and heart failure yet their mechanism of action is still debated. This study was designed to test whether the ACEI captopril increases skin microvascular blood flow by a bradykinin-dependent mechanism. Local changes in microvascular blood flow were measured in the skin of rabbits and of human volunteers using a laser Doppler flow probe. Captopril injected intradermally increased skin blood flow over the dose range of 10(-12)-10(-8) mol site in rabbits and humans. In both species the response was abolished by coinjecting either a nitric oxide synthase (NOS) inhibitor or a cyclooxygenase inhibitor. Intradermal bradykinin also increased rabbit skin microvascular blood flow; at 10(-11) mol site it increased mean +/- SE basal blood flow by 88 +/- 12%. The responses to bradykinin or captopril were abolished by coinjecting a bradykinin antagonist, a specific bradykinin B2 receptor antagonist, or inhibitors of NOS or cyclooxygenase. Injecting a specific angiotensin II receptor antagonist at a dose that antagonized the constrictor effects of exogenous angiotensin II did not cause a significant increase in rabbit skin blood flow. This suggests that endogenous angiotensin II does not influence microvascular blood flow in this model. The results indicate that captopril increases skin microvascular blood flow in rabbits and humans secondary to an increase in endogenous tissue bradykinin; this stimulates B2 receptors with subsequent release of prostaglandins and nitric oxide. ACEIs may increase microvascular perfusion by a bradykinin-dependent mechanism.
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PMID:Captopril increases skin microvascular blood flow secondary to bradykinin, nitric oxide, and prostaglandins. 789 12

Angiotensin converting enzyme (ACE) inhibitors are effective across the whole spectrum of heart failure from mild to severe but there are little data on the use of ACE inhibitors specifically in patients with postinfarct heart failure. Pharmacological properties that might potentially be relevant to the choice of drug after myocardial infarction include differences in metabolism, possession of a sulphydryl group, tissue binding, duration of action, and side effect profile. Of these duration of action is probably the most important, as longer acting drugs generally cause more prolonged first-dose hypotension that shorter acting agents and first-dose hypotension is a particular concern in the early postinfarct period. In the SAVE study captopril was effective in reducing mortality and delaying the onset of symptomatic heart failure after myocardial infarction. Similarly, ramipril reduced mortality in the AIRE study. In contrast, enalapril was largely ineffective in CONSENSUS II. These differences result largely from study design and do not indicate an inherent superiority of captopril or ramipril over enalapril. Nonetheless, a short-acting agent should probably be used for the initial dose in postinfarct heart failure to minimize the risks of prolonged hypotension. This aside, the choice of agent is far less important than appropriate patient selection and appropriate maintenance dosages.
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PMID:Infarct-related heart failure: the choice of ACE inhibitor does not matter. 794 58

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.
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PMID:[Pharmacology of the renin-angiotensin system]. 795 18

GROWTH-PROMOTING EFFECTS OF ANGIOTENSIN: Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular and cardiac growth and may directly influence the pathophysiology of coronary artery disease and ventricular remodeling. Vascular growth occurs when angiotensin activates autocrine and paracrine growth factors, including fibroblast growth factor, transforming growth factor beta-1 and platelet-derived growth factor, and is modulated by endothelium-derived vasodilators and growth inhibitors. ANGIOTENSIN AND CARDIOVASCULAR DISEASE: The presence of angiotensin converting enzyme (ACE) and angiotensin II has been demonstrated in vascular tissue, and these local substances are causally involved in the development of vascular lesions. Similarly, angiotensin can stimulate cardiac myocyte growth and matrix modulation. Cardiac tissue ACE is implicated in ventricular remodeling in the course of progressive heart failure. A genetic variant of the ACE gene has been reported to be associated with increased risks of cardiovascular pathology. ACE INHIBITOR THERAPY: To date, studies of ACE inhibitor treatment in human patients have not demonstrated any prevention of restenosis after angioplasty. However, recent clinical trials in postmyocardial infarction reported that ACE inhibitor therapy reduces recurrent myocardial infarction and prevents cardiac enlargement. Long-term prospective trials are currently being conducted to examine the effects of ACE inhibitor therapy on coronary ischemic events and coronary atherosclerosis, as evaluated by angiography or intravascular ultrasound, and the relationship between coronary events and ACE gene polymorphism.
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PMID:Cell biology and genetics of angiotensin in cardiovascular disease. 796 71

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)
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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)
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PMID:Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. 809 70

Neuroendocrine activation, which begins early after myocardial injury, participates significantly in the pathogenesis of acute myocardial infarction and its complications. Plasma concentrations of catecholamines, arginine vasopressin and atrial natriuretic factor were highest on admission. Activation of the renin-angiotensin-aldosterone system reached its peak after 72 hours. In patients with acute myocardial infarction and heart failure the neuroendocrine activation was more intensively expressed. This study presents clinical consequences of neuroendocrine activation. Its relation to ventricular remodeling, as a potentially maladaptive mechanism is especially discussed. Angiotensin-converting-enzyme inhibitors influence favourably both neuro-endocrine activation and ventricular remodeling after myocardial infarction. At present 7 ongoing extensive multicenter trials are to determine if such a therapy would lead to a better survival and attenuate the progressive deterioration of heart function after myocardial infarction. (Fig. 2, Ref. 24.)
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PMID:[Neurohumoral activation and remodeling after acute myocardial infarct and the effect of angiotensin-converting enzyme inhibitors]. 810 88

Angiotensin converting enzyme (ACE)-inhibitors are established in the treatment of arterial hypertension and heart failure. In recent years ACE-inhibitors have also been used in the treatment of patients with coronary artery disease (CAD), since from experimental data an antiischemic action of these agents is suggested. Antiischemic effects of ACE-inhibitors may be exerted through a reduction of myocardial oxygen demand, by a reduction of angiotensin-mediated coronary vasoconstriction, by an interaction with bradykinin and the prostaglandin system, by a modulation of endothelial control of vascular tone, and by an interaction with the sympathetic nervous system. However, clinical findings on potential beneficial effects of ACE-inhibitors in patients with CAD are inconsistent and controversial. While in hypertensive patients with CAD ACE-inhibitors generally seem to attenuate myocardial ischemia at rest and during exercise, a significant fraction of about 30% of normotensive patients with CAD does not benefit or even deteriorates. Lowering of coronary perfusion pressure and alteration of transmural blood flow distribution may be responsible for this. In patients with left ventricular dysfunction (SOLVD) or congestive heart failure (CONSENSUS, SOLVD) ACE-inhibitors have been proven to prevent progressive deterioration in left ventricular function and to reduce mortality. In patients with asymptomatic left ventricular dysfunction after myocardial infarction (SAVE), long-term administration of captropril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. Therefore, from a prognostic viewpoint patients with CAD and left ventricular dysfunction or congestive heart failure should be treated with ACE-inhibitors, although the clinical use of ACE-inhibitors in patients with ongoing angina pectoris may be limited by an aggravation of angina, presumably due to critically lowering coronary perfusion pressure. Finally, ACE-inhibitors failed to prevent restenosis after successful PTCA. In conclusion, from a prognostic viewpoint patients with CAD and congestive heart failure or left ventricular dysfunction should be treated with ACE-inhibitors. In hypertensive patients ACE-inhibitors generally seem to attenuate myocardial ischemia. In normotensive patients with CAD and angina pectoris but without left ventricular dysfunction ACE-inhibitors cannot generally be recommended at present, unless the patients, which may have benefit from ACE-inhibitor treatment can be better defined.
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PMID:ACE-inhibitors in coronary artery disease? 835 35

Angiotensin converting enzyme (ACE) inhibitors have proved to be valuable, life-saving medications in the management of heart failure. While reducing myocardial oxygen consumption, they increase cardiac output and thus renal plasma flow. Despite reports in the literature of adverse effects of these drugs on renal function, the risks of functional deterioration are predictable in patient populations and remediable. Patients at greatest risk of declining renal function during therapy with ACE inhibitors are those in whom maintenance of renal function is dependent on angiotensin II. Reducing the dose of the concomitant diuretic, liberalizing the dietary intake of sodium, and increasing the dose of the ACE inhibitor usually restores renal function to baseline. In patients with severe renal insufficiency, reducing the dose of the ACE inhibitor might be necessary to preserve the glomerular filtration rate.
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PMID:Renal effects of angiotensin converting enzyme inhibitors in heart failure: a clinician's guide to minimizing azotemia and diuretic-induced electrolyte imbalances. 845 51


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