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)

Homocysteine (Hcy) is a redox active thiol-containing compound with pro-oxidant and pathogenic properties in the cardiovascular system. Angiotensin II (Ang II) also plays important roles in age-associated cardiovascular disease. Recently, the GATA4 transcription factor was recognized as a mediator of heart failure. We investigated the interrelationship of these elements in NIH/3T3 fibroblasts and found that Ang II induces GATA4 activity and Hcy alters Ang II signaling. Electrophoretic mobility shift assays determined that treatment of cells with Ang II induced DNA binding activity to the GATA consensus sequence. This activation was transient with a peak occurring at 30 min. Supershift analysis revealed the GATA binding protein as GATA4. Ang II also induced NFAT activity with similar kinetics. Pretreatment of cells with Hcy (100 microM) delayed the peak of Ang II-induced NFAT and GATA activation to 60 min. Ang II-mediated activation of c-fos serum response factor (SRF) was similarly delayed by Hcy. These results suggest the pathogenic mechanism of Hcy action may be mediated in part via modulation of Ang II-signaling for gene transcription.
 ...
PMID:Modulation of angiotensin II signaling for GATA4 activation by homocysteine. 1122 50

Angiotensin II (ANG II), the effector hormone of the renin-angiotensin system (RAS), has been implicated in the pathophysiology and progression of heart failure. Therefore, the measurement of ANG II has become important to characterize the role of this neurohormone in heart failure. However, because ANG II has been difficult to measure, other components of the RAS have been measured to characterize ANG II production. The RAS components (e.g., renin, angiotensin I-converting enzyme [ACE], angiotensin II) have been measured with a variety of techniques. In this review, RAS physiology and the techniques used to measure the RAS components are discussed. In addition, the advantages and disadvantages of the RAS measurement methods are described.
 ...
PMID:Measurement of the renin-angiotensin system in heart failure. 1123 16

The role of the renin-angiotensin system in the regulation of normal blood pressure and in the pathogenesis of hypertension has long been appreciated. Angiotensin II (Ang II) was originally thought to only influence blood pressure, but the results of many preclinical and clinical studies now suggest that Ang II has an important and distinct role in other cardiovascular pathologies. Drugs that interfere with the renin-angiotensin system, such as angiotensin-converting enzyme (ACE) inhibitors, are now widely accepted for the treatment of chronic renal failure and heart failure. Recent studies have shown that Ang II acts directly on the myocardium to cause ventricular hypertrophy, a response that can be prevented or reversed by selective Ang II type 1 receptor antagonists. The utility of angiotensin receptor antagonists in the treatment of chronic renal failure has been demonstrated, and the results of ongoing clinical trials can be expected to prove their benefit in other cardiovascular pathologies.
 ...
PMID:Experimental and clinical evidence that angiotensin II is an independent risk factor for cardiovascular disease. 1133 62

Prognosis in congestive heart failure is directly linked to neurohormonal activation. Angiotensin II through the activation of the renin angiotensin aldosterone system has been the principal focus therapy over the last 2 decades. New agents that target selective blockade of the angiotensin II receptor have been introduced in clinical trials for the treatment of heart failure. Aldosterone has been identified as a critically important neurohormone with direct detrimental effects on the myocardium. Aldosterone antagonists have been used in clinical trials to improve mortality in patients with chronic heart failure.
 ...
PMID:Angiotensin receptor blockers and aldosterone antagonists in chronic heart failure. 1140 5

Of the population in the United States 65 years of age or older, more than half have high blood pressure. The benefits of treatment are well established, with decreased morbidity and mortality from stroke and MI. Antihypertensive therapy available for the elderly now includes losartan, the prototype of a new class of drugs, the angiotensin II-receptor blockers. The likelihood of even fewer side effects with the angiotensin II-receptor blockers than with ACE inhibitors promises to make them an important new therapy for elderly patients. Angiotensin II is the primary vasoactive component of the renin-angiotensin system, which is implicated in the pathophysiology of hypertension. Influencing this system pharmacologically has, therefore, important consequences for high blood pressure treatment. The ACE inhibitors have had success as antihypertensive agents, but they act early in the renin-angiotensin cascade, possibly leading to unwanted effects. The angiotensin II-receptor blockers act directly at the receptor level, thus avoiding the complications of interrupting the metabolic pathway early and disrupting other hormonal systems. These agents represent a new treatment option for hypertension in the elderly. Other clinical indications, such as heart failure and post-MI, are being investigated.
 ...
PMID:Angiotensin II-Receptor Blockers: Profile of a New Drug Class for Antihypertensive Therapy. 1141 98

Blockade of the renin-angiotensin system by angiotensin converting enzyme (ACE) inhibitors has an established role in the management of hypertension, heart failure, patients post-myocardial infarction and renal impairment. The mechanism of action of angiotensin II antagonists offers the potential of more complete blockade of angiotensin II, selective inhibition of the AT1 receptor and specificity for the renin-angiotensin system. Whether these mechanistic differences enhance the clinical potential of these drugs remains to be established. Preliminary evidence suggests that ACE inhibitors and angiotensin II antagonists have similar antihypertensive, haemodynamic and nephroprotective effects. Several major outcome trials with angiotensin II antagonists are underway and these should determine the eventual clinical potential of this class. Early results suggest equivalence with ACE inhibitors but further direct comparisons are needed. Angiotensin II antagonists have one undisputed advantage--excellent tolerability. Given the continuing under-use of ACE inhibitors because of concerns about adverse effects, this property alone may prove decisive in ensuring that angiotensin II antagonists yield the full clinical potential from blockade of the renin-angiotensin system.
 ...
PMID:Clinical potential: angiotensin converting enzyme inhibitor or angiotensin II antagonist? 1145 Dec 17

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
 ...
PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Angiotensin II Type 1 receptor antagonists share most but not all of their pharmacological actions with angiotensin-converting enzyme inhibitors. The latter belong to standard heart failure therapy, with proven benefit in terms of morbidity and mortality. Promising data have been provided for angiotensin II Type 1 receptor antagonists in experimental models of heart failure. In patients with hypertension and those with diabetic nephropathy, favourable results have been observed with regards to blood pressure control, reversibility of structural changes or prevention of progression of disease. The currently available clinical trials in heart failure patients with angiotensin II Type 1 receptor antagonists suggest that they may be equivalent to angiotensin-converting enzyme inhibitors, but superiority has not been proven. There is no doubt about their effectiveness with regards to symptoms; however, their effect on hospitalisation and mortality is not unequivocally demonstrated. Further trials are warranted, particularly to define their role in comparison with and in addition to angiotensin-converting enzyme inhibitors and to further characterise heart failure patient populations who derive benefit from angiotensin II Type 1 receptor blockers above and beyond angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone.
 ...
PMID:Angiotensin II Type 1 receptor antagonists in chronic heart failure. 1199 51

The effectiveness of ACE inhibitors in reducing morbidity and mortality in patients with heart failure is largely attributable to their suppression of angiotensin II production. Despite chronic therapy with ACE inhibitors, angiotensin II levels may be incompletely suppressed and contribute to the high mortality of patients with heart failure. Recently, angiotensin receptor blockers, which block the effects rather than the production of angiotensin II, have become available. Angiotensin receptor blockers have been evaluated as both monotherapy and in combination with ACE inhibitors. In short term studies, angiotensin receptor blocker monotherapy appears to share many of the hemodynamic and clinical features of ACE inhibitors. In a long-term study, the Losartan Heart Failure Survival Study, angiotensin receptor blockers failed to demonstrate any beneficial effect over that seen with ACE inhibitors. The addition of an angiotensin receptor blocker to an ACE inhibitor appears to exert favorable short term hemodynamic, clinical, and neurohormonal effects. Four ongoing trials, Valsartan Heart Failure Trial, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity, Optimal Therapy in Myocardial Infarction with Angiotensin II Antagonist Losartan study, and Valsartan In Acute Myocardial Infarction study, are evaluating the role of angiotensin receptor blockers either alone or in combination with ACE inhibitors in the management of left ventricular dysfunction. (c)2000 by CHF, Inc.
 ...
PMID:The role of angiotensin receptor blockers in heart failure. 1202 95

Heart failure is a common and disabling condition with a dismal prognosis. Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme (ACE) inhibitors has proven to be a valuable therapeutic strategy in this condition, with well-proven morbidity and mortality benefits. Nonetheless, ACE inhibitors provide incomplete blockade of the RAAS and also inhibit the degradation of bradykinin. Although increased levels of bradykinin may have haemodynamic advantages by contributing to vasodilatation, they may also be largely responsible for some of the adverse effects of ACE inhibitors. Angiotensin II (Ang II) receptor antagonists offer more complete blockade of the RAAS without the potentiation of bradykinin, and it was therefore hoped that they would provide even greater benefits for patients with heart failure. So far, much of the initial promise of the Ang II receptor antagonists in heart failure has not been realised. There has been no conclusive demonstration of their superiority to ACE inhibitors in their effects on morbidity and mortality, and their equivalence to ACE inhibitors has not been proven. The Ang II receptor antagonists have, however, proven to be better tolerated than ACE inhibitors and they are therefore likely to be a reasonable alternative for those patients with heart failure who cannot tolerate ACE inhibition. Recent evidence has indicated that the Ang II type 1 receptor antagonist valsartan is of value when used in patients already receiving either an ACE inhibitor or a beta-blocker, but has also suggested that giving all three drugs together is deleterious. Further evidence about the value of Ang II receptor antagonists in heart failure may be provided by further studies, of which several are currently ongoing.
 ...
PMID:Angiotensin II receptor antagonists in chronic heart failure: where do they fit? 1209 12


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