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

Angiotensin-converting enzyme (ACE) inhibitors have played a highly beneficial role in the therapy of hypertension and congestive heart failure. Detailed analysis of some of the heart failure trials in patients with these diseases has uncovered unexpected benefits in the prevention of cardiovascular events. Paralleling these observations are the rapidly accruing basic studies describing important molecular and cellular effects of these agents. For example, ACE inhibition will prevent stimulation of smooth muscle cell angiotensin II receptors, thereby blocking both contractile and proliferative actions. In addition, ACE inhibition of kininase II inhibits the breakdown of bradykinin. Bradykinin is a direct stimulant of nitric oxide release from the intact endothelial cell. Thus, at the cellular level ACE inhibition shifts the balance of ongoing mechanisms in favor of those promoting vasodilatory, antiaggregatory, antithrombotic, and antiproliferative effects. These effects underlie the potential benefits of ACE inhibition in the therapy of coronary artery disease and atherosclerosis.
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PMID:Emerging concepts: angiotensin-converting enzyme inhibition in coronary artery disease. 911 53

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.
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PMID:Medical treatment of end-stage heart failure. 911 55

Angiotensin-converting enzyme (ACE) inhibitors are widely used in the management of hypertension, heart failure, and nephropathy. It has been suggested that ACE inhibitors containing the sulfhydryl group (SH) have an additional effect on KATP channels. To prove this hypothesis, we studied the effects of the SH-containing ACE inhibitors, captopril and zofenopril, on KATP channel opening of bovine coronary arteries and guinea pig thoracic aortas. Bovine coronary arteries were precontracted with the thromboxane A2 analogue, U46619, and guinea pig thoracic aortas were precontracted with phenylephrine and then relaxed with either captopril or zofenopril (n = 8). Inhibition of KATP channel opening with glibenclamide moderately attenuated the zofenopril-induced relaxation of guinea pig thoracic aorta. However, in the bovine coronary arteries, the relaxing effect of both captopril and zofenopril remained uneffected by glibenclamide. In experiments with enalapril (a non SH-containing ACE inhibitor; n = 6) on guinea pig thoracic aortas, no effect on KATP channels could be seen. From our experiments, we conclude that the postulated opening of KATP channels by SH-group-containing ACE inhibitors contributes little to the vasodilation of guinea pig thoracic aortas caused by ACE inhibitors, and that SH groups have no influence upon KATP channels of bovine coronary arteries.
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PMID:KATP channel opening does not contribute significantly to the vasodilatory effect of SH-group-containing ACE inhibitors. 911 8

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

We have previously shown that nitric oxide (NO) release by the coronary circulation in the failing and nonfailing human heart is, in part, regulated by local kinin production in coronary microvessels. Angiotensin-converting enzyme (ACE) also known as kininase II, inactivates kinins. ACE inhibitors prevent kinin breakdown by ACE, thereby increasing the concentration of bradykinin (BK) and related kinins. The goal of this study was to determine if kinins contribute to the therapeutic action of ACE inhibitors. Six hearts from end-stage heart failure patients were harvested at the time of orthotopic cardiac transplantation. Microvessels were prepared as previously described, and nitrite production, a metabolic product of NO in vitro, was determined by the Griess reaction. Microvessels were incubated in the presence of kininogen and bradykinin, and with the ACE inhibitors ramiprilat, enalaprilat, or captopril. All caused dose-dependent increases in nitrite. For instance, ramiprilat increased nitrite from 76 +/- 5.6 to 155 +/- 15 pmol/min per mg wet weight. Nitrite production in response to ACE inhibition was blocked by N-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, and icatibant (HOE 140), a B2-kinin receptor-specific antagonist. Furthermore, NO production was prevented by 3 different serine protease inhibitors, which block kallikrein, the enzyme responsible for conversion of kininogen to kinins. Our results indicate that ACE/kininase inhibitors increase NO production by the coronary microvasculature in the failing human heart, through increased available active kinins. The therapeutic action of ACE inhibition in the failing human heart may result in part from increased NO production by coronary microvessels.
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PMID:Angiotensin-converting enzyme inhibitors promote nitric oxide production in coronary microvessels from failing explanted human hearts. 929 67

The prevalence of congestive heart failure (CHF), a debilitating condition associated with impaired quality of life and markedly shortened life expectancy, is increasing. The goals of therapy for CHF are reducing symptoms, improving functional capacity, and slowing the progression of the condition. In most cases, this is best achieved with a combination of diuretic and vasodilator therapy. Angiotensin-converting enzyme (ACE) inhibitors have several advantages over other vasodilatory agents and are becoming widely used for treating CHF. The most recently introduced ACE inhibitor, fosinopril, is at least as effective as enalapril, and its dual and compensatory route of excretion is particularly advantageous in patients with renal insufficiency. Fosinopril may also have particular benefits in the prevention of CHF, as it has beneficial effects on cardiac function that may help delay the onset of overt cardiac failure.
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PMID:Treatment of congestive heart failure: experience with fosinopril. 936 86

The endothelium controls vascular smooth muscle tone by secreting relaxing and contracting factors. There is a constant release of endothelium-derived relaxing factors (EDRFs) under basal conditions. In addition, the endothelium can increase the release of EDRFs in response to humoral stimulation by vasoactive substances such as acetylcholine or bradykinin. Under physiological conditions, the most important stimulus to the release of EDRFs is an increase in blood flow leading to increased shear stress on endothelial cells. Recent experimental studies raised the possibility that bradykinin plays an important role in the regulation of vascular tone at rest and during flow-stimulated conditions. Bradykinin is a very potent vasodilator that exerts its vasodilatory actions by causing endothelial release of nitric oxide, prostacyclin and/or a hyperpolarising factor [endothelium-derived hyperpolarising factor (EDHF)]. This concept is also supported by recent studies in humans demonstrating that bradykinin contributes to the regulation of coronary vascular tone under resting and flow-stimulated conditions. This mechanism has now been shown to be important in both human peripheral and coronary arteries. Angiotensin converting enzyme (ACE) inhibitors not only reduce angiotensin II, but also increase bradykinin levels, since the angiotensin converting enzyme is identical to kininase II, an enzyme that degrades bradykinin. This raises the possibility that beneficial vascular effects of ACE inhibitors may be related to increased availability of bradykinin. Indeed, we have recently shown that ACE inhibition improves flow-dependent, endothelium-mediated vasodilation and that this beneficial effect of ACE inhibition is bradykinin dependent. These findings raise the possibility that the beneficial effects of ACE inhibition in heart failure and coronary artery disease might be partly due to improved endothelial function.
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PMID:Endothelial function and bradykinin in humans. 942 44

Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. The renin-angiotensin-aldosterone system is complex and acts as a circulating hormonal system, a local endogenous tissue system and neuromodular. Current experimental evidence suggests that ACE inhibitors reduce the risk associated with atherosclerotic cardiovascular disease. The antiatherogenic action of ACE inhibitors is related to complex effects mediated by these agent, including an antiproliferative and antimitotic action, beneficial effects on endothelial function, plaque-stabilizing effects and the action of these agents on the sympathetic nervous system. The role of ACE inhibitors in preventing the clinical sequale of atherosclerotic cardiac disease has been evaluated in various patient populations. Several small trial assess the effects of ACE inhibitors in severity of angina pectoris have reported conflicting results, with benefit is some patients and no benefit or even exacerbation of angina in others, indicating that ACE inhibitors do not have consistent antianginal effects in short-term study. ACE inhibitors have the theoretical potential to prevent restenosis after PTCA but they do not prevent restenosis and has no effect on overall clinical outcome. New data suggest that ACE inhibitors may be effective therapy fir patients following acute myocardial infarction. The renin-angiotensin system, is activated during new myocardial infarction and has an impact on the process of remodeling of the left ventricle which causes ist dysfunction and heart failure. In most of the large mortality trials the rationale for early treatment with ACE inhibitors after myocardial infarction was stated. ACE inhibitors have a positive effect in preventing the ventricular dilatation and they reduce the rate of reinfarctions and the mortality rate.
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PMID:[The significance of converting enzyme inhibitor angiotensin I to angiotensin II in treatment of patients with coronary disease]. 955 7

The structure and function of subcutaneous small arteries from patients with mild heart failure (n = 27) 6-43 mo after myocardial infarction were compared with vessels from healthy control subjects (n = 10). Patients were randomized to treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril starting 3-10 days after myocardial infarction. Dissected arterial vessels were mounted on a wire myograph for measurement of morphology and isometric tension. Morphology was not different in arteries from the three groups. Responses to norepinephrine, angiotensin II, and electrical field stimulation were similar in arteries from placebo-treated patients with mild heart failure and control subjects. Similarly, endothelium-dependent and -independent relaxation was normal in arteries from patients with mild heart failure. Ramipril therapy was associated with functional alterations: vasoconstrictor responses to norepinephrine and angiotensin II were significantly enhanced compared with placebo (P < 0.001). These data suggest that vascular structure and function are not different in vitro in subcutaneous arteries from placebo-treated patients with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is associated with enhanced vasoconstriction to norepinephrine and angiotensin II, which may reflect upregulation of receptor-mediated events.
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PMID:Structure and in vitro function of human subcutaneous small arteries in mild heart failure. 961 17

Improved understanding of the pathophysiologic course of heart failure has led to many advances in pharmacologic therapy. Angiotensin-converting enzyme inhibitors represent the first effort at targeting neurohormonal activation in chronic heart failure. More recently, beta-adrenergic receptor antagonists have been shown effective in blocking chronic sympathetic nervous system activation. The roles of digoxin and the newer, vasoselective calcium channel blockers in heart failure have been better defined. Other agents targeting the neurohormonal system are under investigation. These include angiotensin-receptor antagonists, aldosterone inhibitors, and endothelin antagonists. Experience with phosphodiesterase inhibitors and adrenergic agents has confirmed the importance of neurohormonal activation in progression of heart failure. Despite angiotensin-converting enzyme inhibitor, diuretic, and digoxin therapy, mortality in heart failure remains high. Careful manipulation of the neurohormonal response to heart failure holds promise for altering the course of the disease.
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PMID:Innovations in the pharmacologic management of heart failure. 963 71


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