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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 is a multifunctional hormone that exerts its effects by interacting will cell surface receptors. Two major subtypes of receptors (AT1 and AT2) have been distinguished by pharmacological and molecular biological techniques. AT1 receptors have been further subdivided into AT1A and AT1B receptors. Several other isoforms have been found, notably in nonmammalian systems, but further information is necessary before definitive classification can be made. AT1 receptors mediate most known functions of angiotensin II, while AT2 receptors may be important developmentally. The molecular, structural, and biochemical characteristics of these receptors have been described, as well as the factors that regulate their expression. This receptor system has been implicated in several cardiovascular diseases, including hypertension, restenosis after angioplasty, cardiac hypertrophy, heart failure, myocardial infarction, and ventricular remodeling. Structural analysis of AT receptors may provide the basis for the development of new therapeutic agents with enhanced specificity for the treatment of these diseases.
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PMID:Angiotensin receptors and their therapeutic implications. 872 91

Our understanding of the renin-angiotensin-aldosterone system (RAAS) has advanced considerably in recent years. The RAAS plays a central role in the control of salt and water balance, and in the regulation of blood pressure and cardiovascular homeostasis. The haemodynamic changes in the period after myocardial infarction stimulate intense activation of both the circulating and the local RAAS. This acts through its end-products, angiotensin II and aldosterone, to promote sodium and fluid retention, and to increase cardiac contractility and systemic vascular tone. There is increasing evidence that, in the long term, this apparently adaptive response may be harmful, and might contribute to the development of some of the complications seen after infarction. Angiotensin II is capable of inducing coronary as well as systemic vasoconstriction, and may therefore prolong the duration of ischaemia. The response of the RAAS after infarction can be modified pharmacologically. Angiotensin converting enzyme (ACE) inhibitor drugs are already the mainstay of treatment in heart failure, and have now been shown to have a crucial role in the prevention of ventricular remodelling after myocardial infarction. Although the precise mechanism of this benefit is unclear, it provides further incentives to develop more effective strategies capable of suppressing neurohumoral activity following infarction.
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PMID:Pathophysiological aspects of the renin-angiotensin-aldosterone system in acute myocardial infarction. 874 65

In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.
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PMID:Consequences of alteration in capillary permeability. 894 69

Angiotensin converting enzyme (ACE) is a key factor in the regulation of two peptide systems: the renin angiotensin system (RAS) and the kinin-kallikrein system (KKS). Since it is involved in the biosynthesis of Angiotensin II (Ang II) as well as in the degradation of bradykinin (BK) it could play an important role in cardiovascular physiology and pathophysiology. ACE is widely expressed in the heart and upregulated in pathophysiological situations such as heart failure and cardiac hypertrophy. In addition, inhibition of ACE has beneficial effects in these conditions. Whereas the regulation of cardiac ACE has been studied extensively, little is known concerning the cellular expression of ACE in cardiac tissue. To define the cellular localization of ACE mRNA expression in the rat heart, we separated coronary microvascular endothelial cells from cardiac myocytes using differential centrifugation and growth on selective media. ACE mRNA expression was measured by a specific polymerase chain reaction assay after reverse transcription (RT-PCR) in different cardiac cells. The studies showed that ACE is differentially expressed in endothelial cells as well as in cardiac myocytes. This differential regulation of ACE in myocytes and non-myocytes may play a role for the diverse actions of the cardiac angiotensin system under physiological and pathological conditions.
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PMID:The cellular basis of angiotensin converting enzyme mRNA expression in rat heart. 895 46

The effects of enalapril on exercise capacity and neurohumoral factors during exercise were evaluated in 10 patients with heart failure. Echocardiograms and exercise testing with expired gas analysis were performed before and after enalapril. Blood samples were obtained before and after exercise. Both ejection fraction and percent fractional shortening increased with enalapril (p < 0.05). The anaerobic threshold and peak VO2 did not change with enalapril. Epinephrine and norepinephrine levels at peak exercise decreased with enalapril (p < 0.1). Plasma renin both at rest and at peak exercise increased with enalapril (p < 0.1). Angiotensin II was lower after enalapril both at rest and at peak exercise (p < 0.1 and p < 0.05, respectively). Aldosterone was lower after enalapril both at rest and at peak exercise (p < 0.05). Atrial natriuretic peptide (ANP) was lower after enalapril both at rest and at peak exercise. There was no significant correlations between peak VO2 and changes in neurohumoral factors before and after enalapril during exercise. In conclusion, neurohumoral changes with enalapril occurred during exercise even if exercise capacity did not improve. Moreover, the improvement of cardiac function at rest and neurohumoral factors with enalapril did not lead to a change of exercise capacity.
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PMID:Effects of enalapril on the exercise capacity and neurohumoral factors during exercise in patients with chronic heart failure. 896 Jun 18

Extracellular matrix (ECM) in the heart and vascular wall includes fibrous proteins and proteoglycans. Fibrous proteins are classified within two categories: structural (collagen and elastin) and adhesive molecules (laminin and fibronectin). These ECM components are important in maintenance of both structure and function of the heart and vascular tissues. Myocardial infarction, hypertrophy, hypertension and heart failure are well known to be associated with progressive cardiac fibrosis. Vascular hypertrophy and thickening has been associated with the pathological series of events that attends both hypertension and restenosis. The accumulation of ECM in the cardiovascular system plays an important role in the development of heart failure after myocardial infarction and hypertension, as well as in vascular hypertrophy and restenosis. Angiotensin II (angiotensin) and transforming growth factor beta 1 are known to play a role in signalling the abnormal accumulation of ECM in these cardiovascular diseases. Administration of angiotensin-converting enzyme inhibitor or angiotensin receptor type 1 antagonist is associated with regression of cardiac hypertrophy and fibrosis as well as vascular hypertrophy.
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PMID:Extracellular matrix and cardiovascular diseases. 898 66

The renin-angiotensin system plays an important role in the pathogenesis of cardiac hypertrophy and chronic heart failure as angiotensin II has been shown to induce cardiac hypertrophy and fibrosis. Besides these structural alterations, functional effects on cardiomyocytes have been reported in different mammalian species. Angiotensin II is known to produce a positive inotropic effect in some species, and differences in atrial and ventricular myocardium have been described. So far, the molecular events which govern angiotensin II-mediated changes in cardiac contractility are not completely understood. In order to study the dependency of the angiotensin II-induced positive inotropic effect on receptor density, we examined the effect of angiotensin II on cardiac function in atria, papillary muscles and isolated ventricular cardiomyocytes from adult Sprague-Dawley rats and TGR(alphaMHC-hAT1) transgenic rats, which expressed the human angiotensin AT1 receptor (hAT1) specifically in the heart. In atrial myocardium from adult Sprague-Dawley rats, angiotensin II (30 micromol/l) produced an AT1-mediated positive inotropic effect (38.5% of control), whereas in papillary muscles and isolated ventricular myocytes, no inotropic response was observed. As shown by polymerase chain reaction (PCR) and radioligand binding, the human angiotensin AT1 receptor was exclusively expressed in transgenic animals, which markedly overexpressed the angiotensin AT1 receptor. However, in transgenic rats the positive inotropic effect in atrial preparations was similar to the controls, and neither in papillary muscles nor in isolated cardiomyocytes the increase in receptor density led to an inotropic effect induced by angiotensin II. These data suggest that the existence of functionally uncoupled receptors rather than the low density of receptors at the ventricular site is responsible for the inability of ventricular myocardium to respond to angiotensin II.
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PMID:Cardiac angiotensin II receptors: studies on functional coupling in Sprague-Dawley rats and TGR(alphaMHC-hAT1) transgenic rats. 922 12

Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tissue RAS's, as well as non-ACE pathways. ACE and other components of the RAS show natural mutations. In this review, we discuss the molecular genetics of the human RAS in relation to cardiovascular disease, including the clinical effects of known ACE molecular variants and possible pharmacological treatment strategies.
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PMID:Molecular genetics of the renin-angiotensin system: implications for angiotensin II receptor blockade. 936 80

The effect of taurine on angiotensin II-induced hypertrophy of cultured neonatal rat heart cells (myocytes and nonmyocytes) was examined. Angiotensin II (1-100 nM) alone caused an increase in the rate of protein synthesis and the surface area of myocytes without altering the rate of DNA synthesis or cell number. It also mediated an increase in DNA synthesis and in cell number of nonmyocytes. Exposure of the cells to taurine (20 mM) in the absence of angiotensin II had no effect on either hyperplastic growth or hypertrophy of the two types of cultured cardiac cells. However, myocytes pretreated with 20 mM taurine exhibited reduced responsiveness to angiotensin II. Following a 24 hr pretreatment with 20 mM taurine, the stimulation in protein synthesis by angiotensin II (1 nM) was significantly suppressed. Similarly, taurine treatment of nonmyocytes reduced the degree of angiotensin II-induced promotion of hyperplastic growth (DNA synthesis and cell number). Finally, taurine partially prevented the rise in [Ca2+]i mediated by angiotensin II in cardiac cells. The present results indicate that taurine is an effective inhibitor of angiotensin II action. The possibility that the beneficial effects of taurine in the treatment of heart failure might be related to its suppression of angiotensin II-mediated cellular responses is discussed.
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PMID:Taurine improves angiotensin II-induced hypertrophy of cultured neonatal rat heart cells. 963 24

Renin, angiotensin II and aldosterone levels are elevated in congestive heart failure, especially when diuretics are introduced. This activation is clearly deleterious by elevating myocardial workload and is related to prognosis of heart failure. The link between hormonal activation and prognosis is causal, as hormonal inhibition by converting enzyme inhibitors improves heart failure prognosis. Angiotensin II and aldosterone appears to be toxic for the myocardium. The results of the trial conducted with angiotensin II antagonist losartan confirm data derived from converting-enzyme-inhibitors trials. The exact role of aldosterone is currently being evaluated in the RALES programme.
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PMID:[Renin-angiotensin-aldosterone system and heart failure: therapeutic aspects]. 977 28


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