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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is recognized that heart failure in patients with atherosclerotic lesion is the result of ischemia. However, there may also be cardiac cell dysfunction independent of ischemia, as factors advancing both of atherosclerosis and heart failure are discovered. The renin-angiotensin system is one of factor and angiotensin-converting enzyme inhibitor (ACEi) prevents progression of atherosclerotic lesion and heart failure. To elucidate the association of atherosclerosis and cardiac cell dysfunction, we investigated the effects of ACEi on cultured cardiac myocytes. Captopril increased beta-receptor density of myocytes and augmented the response to isoproterenol. CV-3480, a ACEi, also up-regulated beta-receptors but angiotensin I, angiotensin II and angiotensin type I receptor antagonist did not. Bradykinin B2 receptor blocker, HOE140, suppressed the effect of captopril on cultured cells. The results suggest that ACEi up-regulated beta-receptors and augmented the response to beta-receptor agonist through BK potentiation.
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PMID:[Association of atherosclerosis and cardiac cell dysfunction]. 895 33

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

Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial remodeling and improve cardiac function after myocardial infarction. We investigated whether the beneficial effects of ACE inhibition were associated with changes in the levels of angiotensin and bradykinin peptides in blood, heart, lung, aorta, and kidney. Rats subjected to coronary artery ligation and selected by ECG criteria to have moderate to large myocardial infarctions (mean size, 38%) were administered perindopril (0, 20, 200, and 2,000 micrograms/kg/day) in their drinking water from the second day after surgery for 26 days. Perindopril caused a dose-related decrease in blood pressure and inhibited the development of both cardiac hypertrophy (estimated by heart weight/body weight ratio) and cardiac failure (estimated by lung weight/body weight ratio). Perindopril inhibited plasma ACE activity and increased plasma renin, with an associated decrease in plasma angiotensinogen. Plasma and all tissues showed a marked reduction in angiotensin II/angiotensin I ratio, indicating effective inhibition of ACE in plasma and tissues. Whereas heart, lung, and kidney showed dose-related decreases in angiotensin II (Ang II) levels, plasma and aortic levels of Ang II were not altered by perindopril. Perindopril increased blood bradykinin levels but did not increase bradykinin levels in heart, lung, aorta, or kidney. Heart showed a 45% increase in bradykinin levels at the highest dose of perindopril, which did not achieve statistical significance, although perindopril reduced the bradykinin(1-7)/ bradykinin-(1-9) ratio in heart, indicating inhibition of cardiac metabolism of bradykinin by perindopril. By contrast, perindopril reduced bradykinin levels in lung. These data support a role for reduced blood pressure and cardiac Ang II levels in mediating the effects of ACE inhibition after myocardial infarction but do not support a role for tissue bradykinin in this process.
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PMID:Effects of angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptides in rats with myocardial infarction. 896 Oct 71

The beneficial effects of angiotensin converting enzyme (ACE) inhibitors in heart failure appear to be independent, at least in part, of their effect on blood pressure. The existence of a local cardiac renin angiotensin system is often suggested as an explanation. It has been known for some time that a substantial proportion of arterially delivered angiotensin I is converted to angiotensin II by ACE of the coronary vascular endothelium. The levels of angiotensin II in cardiac tissue are several times the levels of angiotensin II in circulating blood. Recent evidence suggests that most of the angiotensin II in the heart is not derived from angiotensin I in the circulation, and that most of the angiotensin I in cardiac tissue is generated in the tissue itself. On the other hand, renin mRNA levels are very low or undetectable in the normal heart. In addition, studies on the effects of bilateral nephrectomy on the cardiac tissue levels of renin, angiotensin I, and angiotensin II in pigs have indicated that cardiac renin originates from the kidney and that cardiac generation of angiotensin I and angiotensin II depends on renin from the kidney. Intracardiac synthesis of renin may occur under pathological conditions and during fetal development. The fact that angiotensins are generated by the heart raises the possibility of local mechanisms to regulate the concentrations of these peptides at certain tissue sites. For example, preliminary evidence suggests that binding of renin to cardiac membranes is a mechanism by which renin is taken up by the heart. A specific renin binding protein has been identified in cardiac tissue. Cardiac ACE levels may also influence local angiotensin II formation and are, in part, determined by the so called insertion/deletion ACE gene polymorphism. More detailed knowledge on the site of angiotensin generation and on its regulation will improve our understanding of the role of the renin-angiotensin system in cardiac function, hypertrophy, and postinfarction remodelling.
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PMID:Is there an internal cardiac renin-angiotensin system? 898 64

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

Angiotensin-converting enzyme (ACE) inhibitors are widely used in treating hypertension and chronic heart failure, but their precise sites and mechanisms of the actions are not completely understood. In this study, we evaluated the acute and chronic in vivo inhibition of ACE by perindopril in both the endothelium and adventitia of large blood vessels including the aorta, carotid, and femoral arteries, heart, lung, and kidney by using in vitro autoradiography with [(125)I]351A as a ligand. After short-term (0.1, 0.3, and 1 mg/kg) or long-term oral administration (0.3 mg/kg), perindopril significantly inhibited plasma ACE (p < 0.001), the plasma angiotensin II (Ang II)/Ang I ratio (p < 0.01), and decreased mean arterial pressure (p < 0.001) in a dose-related manner. In the aorta, carotid, and femoral arteries, free ACE was inhibited to a similar extent in both the endothelium and adventitia by perindopril, in a dose-dependent manner, whereas total ACE in both layers of these vessels was unaltered. Similar short- and long-term ACE inhibition by perindopril was observed in the lung and heart, with somewhat greater inhibition of kidney and plasma ACE. Vascular and tissue ACE inhibition correlated highly with both plasma ACE and the plasma Ang II/Ang I ratio (r = 0.63-0.89; p < 0.001). Whereas the effects of perindopril on blood pressure, plasma Ang II/Ang I ratio, plasma and vascular ACE were all highly dose dependent, there were no significant differences on the degree of ACE inhibition observed between the three large blood vessels or between their adventitial and endothelial layers. These results demonstrate that perindopril readily penetrates the vascular wall after short- or long-term oral administration, and in a dose-dependent manner, potently inhibits both endothelial and advential vascular ACE to a comparable degree. Therefore ACE inhibitors may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.
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PMID:Acute and chronic in vivo inhibition of angiotensin-converting enzyme by perindopril in the endothelium and adventitia of large arteries and organs of the rabbit. 912 66

Atherosclerosis and its consequences account for most of the morbidity and mortality in Western countries. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it has become clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation, and vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the intima, as well as increased contraction, migration and proliferation of vascular smooth muscle cells. One of the enzymes with a key role in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located on the endothelial cell membrane and is responsible for the conversion of angiotensin I into angiotensin II, as well as for the breakdown of bradykinin. While the antihypertensive effect of ACE inhibitors probably contributes to their antiatherogenic effects, other mechanisms are likely to be of greater importance. These direct antiatherogenic effects attributable to ACE inhibition are related to their vasculoprotective properties, including antiproliferative and antimitogenic activity, effects on endothelial function, protection against plaque rupture, antithrombotic effects, and possible antioxidant properties. There is overwhelming evidence to demonstrate the beneficial effects of long-term ACE inhibitor treatment in heart failure, acutely for suspected myocardial infarction (MI), and following MI in patients with left ventricular dysfunction. Hypercholesterolemia is a health risk, and epidemiological studies have shown a line between total cholesterol levels and the risk of cardiac events. Studies have shown that lowering the levels of total and low-density lipoprotein cholesterol using HMG-CoA reductase inhibitors can result in a decrease in cardiac morbidity and mortality. Angiographic studies of coronary arteries have demonstrated a disparity between the decrease in cardiac events and the extent of regression of coronary artery lesions. Mechanisms other than the regression of coronary stenosis may therefore be important in the beneficial effect of cholesterol lowering. It may be of major importance that lipid-lowering therapy is associated with improved endothelial function and decreased platelet activity. Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective properties which may explain their beneficial effects on cardiovascular morbidity and mortality.
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PMID:[Pharmacotherapy of arteriosclerosis and its complications. Effect of ACE inhibitors and HMG-CoA-reductase inhibitors]. 919 90

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


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