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)

Captopril, the classic inhibitor of the angiotensin converting enzyme, was employed in several large clinical studies in recent years. The effect of captopril was compared either with placebo, or captopril was selected as the reference ACE inhibitor for comparison with another therapy. In the classic study SAVE, captopril administered to patients after myocardial infarction with a dysfunction of the left chamber reduced mortality by 19%. Though in the study ELITE the AT1 blocker losartan was more effective to reduce mortality in patients with chronic heart failure than captopril, the larger and mortality-oriented study ELITE II did not demonstrate a difference in mortality reduction between captopril and losartan. ACE inhibitors thus remain drugs of choice in chronic heart failure. AT1 blockers are to be used in the cases when ACE inhibitors are not tolerated. The study CAPPP has demonstrated that captopril in hypertonic patients not only effectively decreases blood pressure but exerts a similar effect on mortality reduction as the classic treatment with a diuretic and a betablocker, the most effective being captopril in diabetic patients. Administration of captopril in hypertonic patients with diabetes mellitus in the study UKPDS had an effect on mortality reduction as well as micro- and macrovascular complications of diabetes similar to that of atenolol. The ongoing study VALIANT compares the AT1 blocker valsartan or a combination of valsartan and captopril with captopril alone on patients at risk after myocardial infarction. Also at the beginning of the 21st century captopril maintains a stable position in the treatment of the cardiovascular system.
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PMID:[The ACE inhibitor, captopril, in the light of new clinical studies]. 1192 78

Kinins are vasodilator peptides implicated in many physiological and physiopathological processes such as blood pressure regulation and that of the coronary circulation and inflammatory reactions. Kinins play an essential role in ventricular function as they counteract the effects of angiotensin II during myocardial ischaemia, ventricular remodelling and severe cardiac failure, emphasising the value of treatment favouring local endogenic production of bradykinin such as ACE inhibitors, neutral endopeptidase inhibitors and antagonists of AT1 receptors of angiotensin II.
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PMID:[Bradykinin and ventricular function]. 1199 32

ACE-inhibitors and AT, receptor antagonists play an important role in the treatment of cardiovascular and renal diseases. The criteria of evidence-based medicine indicate that ACE-inhibitors (in appropriate combinations with other cardiovascular agents) continue to represent the treatment of first choice in chronic heart failure, post-myocardial infarction with compromised ventricular function, high cardiovascular risk, and diabetic (type 1) nephropathy. It is here that the AT1 antagonists should be used--in particular when ACE-inhibitors are not tolerated. The AT1 antagonists, Irbesartan and Losartan, are applied, at appropriately high doses, primarily in hypertensives with diabetic (type 2) nephropathy. With the current exception of chronic heart failure, no confirmed data are yet available on the value of combination treatment. The LIFE study has shown that an AT1 antagonist is superior to an established beta blocker in hypertensives with an increased risk (left-ventricular hypertrophy), in particular when diabetes mellitus is impending or already present.
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PMID:[ACE inhibitor or AT1 antagonist. Is there a differential therapy?]. 1213 23

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.
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PMID:Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension. 1213 27

Chronic pharmacotherapy of congestive heart failure deals with its special pathophysiology and acts on different sites of the cardiorenal axis. The standard-therapy consists of diuretics, ACE-inhibitors and beta-blockers and can be supplemented by cardiac glycosides, if heart failure worsens. Cardiac glycosides are also administered if tachycardic arrhythmias occur. Aldosterone-antagonists are combined with standard therapy in NYHA III - IV to counteract cardiac remodelling. AT1-antagonists are indicated when ACE-inhibitors are contraindicated or cannot be administered because of side-effects. Combination with ACE-inhibitors and AT1-antagonists may be of benefit for the patient since morbidity and hospitalization decrease.
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PMID:Pharmacotherapeutic strategy in heart failure. 1222 21

Atherosclerosis is associated with increased angiotensin II AT1-receptor expression and vascular hyperresponsiveness to angiotensin II. Nevertheless, atherosclerosis is often not accompanied by hypertension. We studied if the hypertensive effect of angiotensin II is more pronounced in atherosclerosis. Rabbits were fed a high-cholesterol diet (n = 10) for 12 weeks, followed by a standard diet for another 6 weeks. Control animals received the standard diet (n = 8) for 18 weeks. After 18 weeks, haemodynamic measurements were performed during a baseline recording and during an intravenous infusion of angiotensin II (0.4 microg kg-1 min-1). Atherosclerosis in the high-cholesterol group was verified by histological and lipidchemical tissue examinations. During angiotensin II infusion, total peripheral resistance (TPR) increased more in the high-cholesterol group than in controls (+81.6 +/- 12.4 vs. +40.6 +/- 9.7 mmHg min L-1, P < 0.05). While cardiac output and stroke volume (SV) decreased more in the high-cholesterol group (P < 0.05), reflex bradycardia was stronger in the control group (P < 0.05), indicating a reduced baroreceptor reflex sensitivity in atherosclerosis. Despite the larger increase in TPR and the reduced baroreceptor reflex sensitivity in the high-cholesterol group, maximum blood pressure response to angiotensin II was similar in both groups. The lack of a greater blood pressure response to angiotensin II in the high-cholesterol group could be the result of the early stages of heart failure. Under resting conditions, heart failure seems to be fully compensated, as baseline haemodynamic parameters were similar in the high-cholesterol group and in controls. However, during angiotensin II infusion, the compensatory mechanisms do not prevent a stronger fall in cardiac output and SV. Therefore, the blood pressure response to angiotensin II is not exaggerated in atherosclerotic animals, as vascular hyperresponsiveness to angiotensin II is opposed by the stronger fall in cardiac output and SV.
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PMID:Cardiovascular responses to angiotensin II in atherosclerosis. 1235 68

Heart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG II effects may be particularly important in these situations is the nucleus of the solitary tract (NTS). Located in the dorsomedial medulla, the NTS is the termination site of baroreceptor afferents and is essential for mediating the baroreflex. In hypertensive animals the baroreflex is impaired; this may be reversed by antagonizing ANG II AT1 receptors in the NTS. Recently, we showed that the baroreflex depressant action of ANG II in the NTS is mediated by activation of endothelial nitric oxide synthase (eNOS) and enhanced release of GABA. Using conventional pharmacological tools and a range of adenoviral-mediated expression of dominant negative proteins, we have determined the intracellular pathway(s) in the NTS by which ANG II activates eNOS. Our data indicate that ANG II acting in the NTS depresses the baroreflex via a Gq protein-mediated activation of phospholipase C, which through 1,4,5-inositol triphosphate causes release of calcium from the IP3-sensitive intracellular stores and calcium-calmodulin formation. In contrast, multiple site disruption of a pathway leading to eNOS activation via the serine/threonine kinase Akt was ineffective
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PMID:Genetic and pharmacological dissection of pathways involved in the angiotensin II-mediated depression of baroreflex function. 1237 82

In many types of cardiovascular pathophysiology such as hypercholesterolemia and atherosclerosis, diabetes, cigarette smoking, or hypertension (with its sequelae stroke and heart failure) the expression of endothelial NO synthase (eNOS) is altered. Both up- and downregulation of eNOS have been observed, depending on the underlying disease. When eNOS is upregulated, the upregulation is often futile and goes along with a reduction in bioactive NO. This is due to an increased production of superoxide generated by NAD(P)H oxidase and by an uncoupled eNOS. A number of drugs with favorable effects on cardiovascular disease upregulate eNOS expression. The resulting increase in vascular NO production may contribute to their beneficial effects. These compounds include statins, angiotensin-converting enzyme inhibitors, AT1 receptor antagonists, calcium channel blockers, and some antioxidants. Other drugs such as glucocorticoids, whose administration is associated with cardiovascular side effects, downregulate eNOS expression. Stills others such as the immunosuppressants cyclosporine A and FK506/tacrolimus or erythropoietin have inconsistent effects on eNOS. Thus regulation of eNOS expression and activity contributes to the overall action of several classes of drugs, and the development of compounds that specifically upregulate this protective enzyme appears as a desirable target for drug development.
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PMID:Regulation of endothelial-type NO synthase expression in pathophysiology and in response to drugs. 1238 13

The AT1 receptor blocker(ARB) has differential pharmacological merits from the ACE inhibitor, and is expected to be the promising agent for treatment of various cardiovascular diseases such as heart failure and nephropathy, as well as hypertension. Three ARBs, losartan potassium, candesartan cilexetil and valsartan, have been already clinically used in Japan. In the near future, several new ARBs, including telmisartan, ormethartan and irbesartan, are expected to become available for clinical use. In this review, pharmacological properties and future view of each ARB are described and discussed.
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PMID:[Tendency and prospect of the development of new ARBs]. 1239 78

In the course of cardiac diseases, various neuruhomonal systems in the plasma are activated. So far there have been only isolated results of investigations about the functional state of central neuropeptide systems in cardiac diseases and, in particular, in heart failure. We investigated, therefore, the central vasopressinergic system, an important neuropeptide system in cardiocirculatory regulation in a model of myocardial hypertrophy and left ventricular dysfunction, a model of supravalvular aortic stenosis. In addition to increased vasopressin concentrations in plasma, central vasopressin is also altered in this model. A differential stimulation of vasopressin in the hypothalamic areas and in the areas of the brain stem that are involved in central cardiocirculatory regulation was detected. Reduced vasopressin concentrations in the locus coeruleus, an important regulatory area of sympathetic nervous activity, suggest a central regulatory mechanism through which stimulation of the sympathetic nervous activity can be prevented. Our investigations showed that non-osmotic factors like the baroreceptor reflex and angiotensin II, are important stimuli of the vasopressinergic system. We were also able to show that the central vasopressinergic system in rats with experimental heart failure and myocardial hypertrophy is inhibited by treatment with an ACE inhibitor and AT1 receptor antagonist. As seen with autoradiography, this effect is mediated by a central effect of the drugs. Research into central regulatory mechanisms in cardiovascular diseases is, on the one hand, of crucial importance to our understanding of complex pathophysiological processes, and on the other hand, it serves the development of new therapeutic approaches with the goal of influencing these mechanisms directly pharmacologically and for the elucidation of central, currently unknown effects of cardiovascular drugs.
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PMID:The central vasopressinergic system in experimental left ventricular hypertrophy and dysfunction. 1243 42


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