Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic heart failure (CHF) is characterized by sympathoexcitation, and the cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex. Our previous studies have shown that the CSAR was enhanced in CHF. In addition, central angiotensin II (ANG II) is an important modulator of this reflex. This study was performed to determine whether the CSAR evoked by stimulation of cardiac sympathetic afferent nerves (CSAN) in rats with coronary ligation-induced CHF is enhanced by ANG II in the paraventricular nucleus (PVN). Under alpha-chloralose and urethane anesthesia, renal sympathetic nerve activity (RSNA) was recorded. The RSNA responses to electrical stimulation (5, 10, 20, and 30 Hz) of the CSAN were evaluated. Bilateral microinjection of the AT1-receptor antagonist losartan (50 nmol) into the PVN had no significant effects in the sham group, but it abolished the enhanced RSNA response to stimulation in the CHF group. Unilateral microinjection of three doses of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to stimulation. Although ANG II also potentiated the RSNA response to electrical stimulation in sham rats, the RSNA responses to stimulation after ANG II into the PVN in rats with CHF were much greater than in sham rats. The effects of ANG II were prevented by pretreatment with losartan into the PVN in CHF rats. These results suggest that the central gain of the CSAR is enhanced in rats with coronary ligation-induced CHF and that ANG II in the PVN augments the CSAR evoked by CSAN, which is mediated by the central angiotensin AT1 receptors in rats with CHF.
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PMID:ANG II in the paraventricular nucleus potentiates the cardiac sympathetic afferent reflex in rats with heart failure. 1547 55

Chronic heart failure with its age-dependent prevalence and incidence is one of the most frequent diseases. Due to high mortality and morbidity there is the necessity of early diagnosis and therapeutic measures being as causal as possible. The medical graded therapy is based on the combination of ACE-inhibitors/AT1-blockers, beta-blockers, diuretics and digitalis. Cardiac resynchronization therapy represents a novel option of treatment for only 25% of patients. Nevertheless the prognosis of patients with chronic heart failure with conventional medical therapy is remaining poor. Additional improvement in the treatment of patient with chronic heart failure remains a priority medical task. The results of this case report argues for CPAP as further adjunctive treatment option in patients with chronic heart failure.
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PMID:[CPAP as adjunctive treatment option for chronic heart failure]. 1624 Jan 42

Chronic heart failure is one of the most common diseases in internal medicine. Systolic and diastolic heart failure can be distinguished. According to the guidelines therapy consists of beta-blockers, ACE inhibitors/AT1 receptor antagonists, diuretics, aldosterone antagonists, and glycosides. Older patients should also be treated following the guidelines. However, side effects and interactions between drugs are more frequent and require special attention. The majority of concomitant diseases are no contraindication to heart failure treatment.
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PMID:[Therapy of heart failure in the elderly]. 1680 19

Chronic heart failure is an increasingly frequent clinical syndrome, characterized by reduced physical performance, dyspnea and an adverse prognosis. It is associated with age, indicating that it will become more common. Diagnosis requires the characterization of cardiac dysfunction and a precise definition of the underlying cardiac disease. Treatment guidelines of the cardiac societies, which were updated 2005, recommend therapy with ACE-inhibitors, AT1 receptor antagonists, beta-blockers, aldosterone antagonists and digitalis. It is essential, however, to consider the individual circumstances such as underlying disease, age as well as the frequent complications and comorbidities.
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PMID:[Therapy of chronic left heart failure]. 1717 82

Chronic heart failure may be caused by systolic pump failure and/or impairment of diastolic filling of the ventricles. The standard pharmacotherapy for systolic heart failure includes an ACE inhibitor, betablocker, diuretics and, in patients with severe symptoms, a low dose aldosterone antagonist. An AT1 receptor blocker is indicated for those patients who do not tolerate ACE inhibitors. If patients remain in the functional class NYHA III-IV despite optimal medication and have cardiac dyssynchrony, biventricular pacing may improve the symptoms and prognosis. While evidence-based treatment significantly reduces morbidity and mortality in systolic heart failure, hardly any results from clinical trials are available for diastolic heart failure. Therefore, therapy in patients with diastolic heart failure remains in most cases empirical.
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PMID:[Guideline satisfying therapy for chronic heart failure]. 1761 26

Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction. Age- and sex-matched mice from both strains subjected to sham operation served as controls. One group of WT animals subjected to myocardial infarction was treated with antagonist of AT1 receptor telmisartan over 12 weeks. Abundance and localization of CCN1 protein in kidney were assessed with Western blotting and immunohistochemistry, respectively. In all groups the strongest immunohistochemical reaction for CCN1 was observed in distal convoluted tubules and in smaller arteries, however, the total expression of CCN1 protein was lower in IL-6 KO mice in comparison to WT animals. The main difference in CCN1 distribution between the examined genotypes was lack of reaction in internal renal medulla and very weak reaction in proximal convoluted tubules in IL-6 KO mice. Experimental heart failure only slightly attenuated the expression of CCN1 protein in the kidney of WT mice and had no effect in IL-6 KO mice. Although, blockade of AT1 receptor did not alter CCN1 protein expression in kidneys of WT mice after myocardial infarction, it significantly changed its CCN1 distribution in the renal tubular system.
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PMID:CCN1 expression in interleukin-6 deficient mouse kidney in experimental model of heart failure. 2369 Feb 22

Chronic heart failure is a crucial problem of current cardiology. Despite that, no major development has occurred in the therapy in recent years. In this regard, first results of studies with ARNI inhibitors (angiotensin-receptor neprilysin inhibitors) may be considered hopeful. Dual inhibition of AT1 receptors and neprilysin blocks renin-angiotensin-aldosteron (RAS) axis and concurrently supports natural vasodilatory and diuretic effect of natriuretic peptides. Large-scale prospective randomized multicenter trial PARADIGM-HF with more than 8000 individuals with stabilized chronic heart failure with systolic dysfunction (LV EF 40%, later 35%), mostly in functional class NYHA II-III with elevated BNP/NT-pro BNP has shown 20% decrease in primary endpoint (cardiovascular death or hospitalization for heart failure) in a group treated by ARNI (LCZ696; sacubiltril - valsartan). Beneficial effect of ARNI was consistent also for total and cardiovascular mortality, for hospitalization for heart failure and in other pre-specified subgroup analyses, including quality of life. The treatment was safe, typical adverse event was hypotension, however without a need to interrupt the treatment. Dual RAS and neprilysin inhibition might thus after long time become a change in stable chronic heart failure with systolic dysfunction treatment "paradigm". Czech Republic significantly contributed to this study and all study sites should be congratulated and thanked for their high-quality work provided.
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PMID:[Study PARADIGM-HF - a paradigm shift in the treatment of chronic heart failure]. 2675 Jun 22

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.
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PMID:Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade? 2809 51