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

Angiotensin II type I receptor antagonists (ARAs) have been tested in two large randomized trials, Evaluation of Losartan in the Elderly II (ELITE II) and the Valsartan Heart Failure Trial (Val-HeFT), and several other large trials are ongoing in the indication of chronic heart failure (CHF). Based on the available evidence, angiotensin converting enzyme inhibitors remain the cornerstone in the treatment of CHF. However, much more information should be available in the next few years, which will provide more evidence on how to use ARAs and in which patients.
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PMID:Are angiotensin II receptor antagonists indicated in chronic heart failure? 1263 89

Angiotensin II (AngII) plays a critical role in control of cardiovascular and renal homeostasis. In addition to its physiological action as a vasoconstrictor, growing evidence supports the notion that AngII contributes to cardiovascular diseases such as hypertension, atherosclerosis, and heart failure. The physiological and pathological actions of AngII in adults are mediated largely via the AngII type 1 receptor (AT1R), a heterotrimeric G-protein-coupled receptor (GPCR). Besides coupling with heterotrimeric G proteins to activate phospholipase C-beta (PLC-beta), AT1R also activates receptor tyrosine kinases (PDGF-R, EGF-R and IGF-R) and non-receptor tyrosine kinases (Src, Fyn, Yes, proline-rich tyrosine kinase 2 (Pyk2), focal adhesion kinase (FAK) and JAK2). These tyrosine kinases play critical roles in AngII-stimulated cell signal events.
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PMID:Angiotensin II signaling pathways mediated by tyrosine kinases. 1267 64

Taurine, an amino acid that exhibits anti-angiotensin II and osmoregulatory activity, is found in very high concentration in the heart. When the intracellular content of taurine is dramatically reduced, the heart develops contractile defects and undergoes an eccentric form of hypertrophy. The development of myocyte hypertrophy has been largely attributed to angiotensin II, whose growth properties are antagonized by taurine. Overt heart failure is usually associated with myocyte death, including death due to angiotensin II-induced apoptosis. However, the effect of taurine deficiency on angiotensin II-induced apoptosis has not been examined. To investigate this effect, taurine-deficient cells, produced by incubating rat neonatal cardiomyocytes with medium containing the taurine transport inhibitor, beta-alanine, were exposed to angiotensin II. The peptide increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase 9 activation more in the taurine-deficient than the normal cell. Angiotensin II also promoted the translocation of protein kinase C (PKC)epsilon and PKCdelta, the expression of Bax, and the activation of c-Jun N-terminal kinase (JNK), effects that were greater in the taurine-deficient cell. However, the data ruled out a role for extracellular signal-related kinase (ERK), Bad, and p38 mitogen-activated protein kinase in the beta-alanine-angiotensin II interaction. Because PKC and JNK affect the expression and phosphorylation state of certain Bcl-2 family members, they appear to contribute to the potentiation of angiotensin II-induced apoptosis by taurine deficiency.
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PMID:Possible cause of taurine-deficient cardiomyopathy: potentiation of angiotensin II action. 1271 6

The local renin-angiotensin system in cardiac tissue has been demonstrated to be involved in the pathophysiology of cardiac hypertrophy and heart failure. Angiotensin II type 1(AT1) receptor stimulation leads to vasoconstriction, cell growth, oxidation, aldosterone release, and fibrosis. Recent evidence suggests that angiotensin II type 2(AT2) receptor exerts cardioprotective effects by counteracting against AT1 receptor. However, the role of AT2 receptor signaling in cardiac hypertrophy and fibrosis still remain controversial. This review focused on the accumulating evidence for the cardiac renin-angiotensin system in heart failure.
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PMID:[Renin-angiotensin system and heart failure]. 1275 98

Diastolic dysfunction is now recognized as an important mechanism of heart failure, but treatment for diastolic failure has not yet been established. Many of causes for diastolic dysfunction have been related to myocardial hypertrophy or fibrosis. Until recently, angiotensin II has been proposed as one of important growth factors that lead into hypertrophy and fibrosis. Angiotensin II blockade, therefore, is a promising candidate for the treatment of diastolic failure. Two randomized studies with angiotensin II type 1 receptor blocker are under way. This review will describe the pathophysiologic basis for diastolic dysfunction, and discuss the possible treatments for diastolic failure referring to the recently-proposed two guidelines.
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PMID:[Treatment for diastolic failure]. 1275 15

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

Angiotensin II, a potent vasoconstrictor, is mainly present in the vascular endothelium. Multiple studies have confirmed that angiotensin-converting enzyme (ACE) inhibitors, which block the formation of angiotensin II, lower blood pressure and also improve heart failure. These agents not only have beneficial hemodynamic effects but also bestow additional benefits on vascular function and prevent clinical cardiovascular events in patients at risk for coronary artery disease. These latter benefits may represent effects of ACE inhibitors on local endocrine pathways, inflammatory processes, and atherosclerosis taking place within the arterial wall. Current evidence suggests that, although ACE inhibitors may not substantially reverse atherosclerotic plaque already present, they may slow the progression of such atherosclerotic lesions. In addition, by modulating inflammatory pathways within and adjacent to the atherosclerotic lesion, they may stabilize an unstable plaque and therefore decrease the risk of plaque rupture and its complications.
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PMID:Can angiotensin-converting enzyme inhibitors reverse atherosclerosis? 1293 84

The recent years have witnessed tremendous advances in the understanding of the pathophysiology of chronic heart failure (CHF), leading to significant improvement in therapy. Recognition of the deleterious effects of angiotensin II is an major therapeutic target. By blocking the transformation of angiotensin I to angiotensin II, angiotensin-converting enzyme inhibitors (ACEI) improve symptoms, exercise tolerance and survival at all stages of CHF. Angiotensin II-receptors blockers (ARB) have several theoretical advantages over ACEI, including a better tolerance profile, that may lead to a more favourable effect. In CHF with systolic dysfunction, randomised-controlled trials comparing losartan to captopril (ELITE 1 and ELITE 2) or valsartan versus placebo on top of conventional therapy (Val-HeFT) failed to demonstrate a superiority of ARB's compared to ACEI in terms of mortality. However, ARB's appeared better tolerated in this indication. The treatment of CHF with preserved systolic function remains unclear and may be defined in a near future by two studies addressing the role of on candesartan (CHARM study) or irbesartan (I-Preserve study) in this form of CHF. ACEI and beta-blockers remain on first line for treating CHF due to systolic dysfunction. Losartan or valsartan can be considered as an alternative if ACEI are not tolerated or contraindicated.
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PMID:[ACE inhibitors and/or sartans in heart failure: is there a difference?]. 1460 88

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 micromol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 micromol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.
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PMID:Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro. 1461 77

Endothelial dysfunction might be related to an increase in superoxide anion production in patients with hypertension, hypercholesterolemia, diabetes mellitus, and heart failure. Studies in animal models indicate that angiotensin II increases superoxide anion production by vascular tissues. We examined whether angiotensin II attenuates endothelium-dependent vasodilation via an increase in superoxide anion production in human forearm vessels in vivo. Forearm blood flow was measured in 23 healthy young men. We examined forearm vasodilator responses to an intra-arterial infusion of acetylcholine (4, 8, and 16 microg/min) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min) before and during an intra-arterial infusion of anglotensin II (n=8), angiotensin II plus vitamin C (n=8), and vitamin C alone (n=4). Angiotensin II attenuated the forearm vasodilatory response to acetylcholine (p<0.05), and this attenuated response was abolished by vitamin C. Angiotensin II did not alter the forearm vasodilatory response to sodium nitroprusside, and vitamin C infusion did not affect the forearm vasodilatory response to either acetylcholine or sodium nitroprusside. The forearm vasodilator response to acetylcholine did not change during infusion of norepinephrine (n=3), which reduced forearm blood flow to a degree similar to that by angiotensin II infusion. These results suggest that angiotensin II attenuates endothelium-dependent forearm vasodilation, and vitamin C improves this impairment. Thus, angiotensin II likely attenuates endothelium-dependent vasodilation via an increase of superoxide anion production in the human forearm in vivo.
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PMID:Vitamin C improves attenuated angiotensin II-induced endothelium-dependent vasodilation in human forearm vessels. 1471 37


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