Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are now numerous angiotensin converting enzyme (ACE) inhibitors under development, clinical trial or in clinical use for cardiovascular disease, a situation analagous to the beta blockers. They currently vary in their chemical and physical structure, whether they contain a sulphydril group or are pro-drugs, and in their pharmacokinetics. Whether these differences will convey any special or particular clinical advantages to individual ACE inhibitors has yet to be established. Further research is necessary to determine whether tissue ACEs are merely isoenzymes or whether they differ in their functional properties. Different bioavailability in tissues of the individual ACE inhibitors could confer differing pharmacodynamic properties. ACE inhibitors have been a major advance in the treatment of hypertension and heart failure. In heart failure they have been shown to improve the haemodynamics, to improve symptoms, and most recently, to prolong survival. In hypertension, ACE inhibitors have some physiological advantages over current antihypertensive agents. They have several favourable cardiovascular effects without metabolic disadvantages which provide a theoretical basis for cardio-protection in hypertensive patients.
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PMID:Angiotensin converting enzyme inhibitors: differences and advantages for first line therapy in hypertension. 267 52

Persons with persisting (at least 3 measurements over several weeks) borderline blood pressure elevation or established hypertension should always be instructed to follow general non-pharmacological measures. Antihypertensive pharmacotherapy is recommended in the following situations: in hypertensive emergencies, immediately; if the hypertension is not due to a surgically remediable cause, in patients with documented (at least 3 measurements) blood pressure elevation to diastolic values greater than 100 mm Hg; in patients with "mild" hypertension (diastolic up to 104 mm Hg) which does not decrease to less than 160/95 mm Hg following 3 to 6 months of treatment with general non-pharmacological measures; in persons with borderline blood pressure values (141-159/91-94 mm Hg) that persist following 6 to 12 months of general measures and only if they have severe additional cardiovascular risk factors; in patients with pronounced isolated systolic hypertension (greater than 180 mm Hg). In elderly patients who are frail or have evidence of advanced cardiovascular disease, dementia or other debilitating illnesses, blood pressure-lowering drugs should generally be reserved for diastolic blood pressure values consistently exceeding 110 mm Hg. There have recently been important new developments in antihypertensive pharmacotherapy. Two new pharmacological principles, the calcium entry blockers and angiotensin converting enzyme (ACE) inhibitors, have been introduced widely into practical hypertension treatment. On the other hand, concern has arisen that the conventional, thiazide-diuretic based therapy, despite its established beneficial influence on blood pressure and most cardiovascular complications, may not significantly improve or may sometimes even adversely affect coronary prognosis because of metabolic side effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hypertension management in practice, 1986]. 287 92

Since the discovery of the atrial natriuretic factor (ANF) an endocrine function has been attributed to the mammalian heart. This function may include definition of optimal conditions for efficient performance of the heart, e.g. by reduction of afterload in hypertension or of preload and afterload in heart failure. Plasma ANF levels were measured in various cardiovascular disease states and compared with those of controls and of patients with liver cirrhosis. Plasma ANF levels in hypertensive patients were sevenfold higher than in controls, and in patients with heart failure 40-fold higher than normal values. Small differences were detected between controls and patients with cirrhosis of the liver, in spite of the impaired renal sodium handling seen in cirrhotics. Plasma ANF levels were significantly correlated with haemodynamic parameters and were inversely related to the cardiac index. Treatment with an angiotensin converting enzyme inhibitor led to a significant decrease in plasma ANF levels in parallel with the haemodynamic improvement. Preliminary chromatographic analysis suggested differences in the structure of plasma ANF between normotensive and hypertensive subjects.
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PMID:Atrial natriuretic factor in plasma of patients with arterial hypertension, heart failure or cirrhosis of the liver. 294 36

Although the therapeutic usefulness of angiotensin converting enzyme (ACE) inhibitors in patients with hypertension and congestive heart failure has been clearly demonstrated, important unanswered questions remain about these drugs, including patient selection criteria, side effects, long-term effects, and especially their precise mechanism of action. The principal explanation of the effect of ACE inhibitors remains the inhibition of the renin-angiotensin system (RAS). However, in chronic treatment with ACE-inhibitory drugs, this relationship may not held true. Additional mechanisms of action postulated to explain the effect of ACE-inhibitors include inhibition of angiotensin II formation in the central RAS, neutralization of renin activity in the vascular wall, blockade of vasoconstrictor response to sympathetic nerve stimulation, and possible involvement of prostaglandins linked, for instance, to bradykinin accumulation. The search for additional mechanisms of action should lead to clinically important findings, provide a better understanding of the pathophysiology of cardiovascular disease, and improve patient treatment with ACE inhibitory drugs.
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PMID:Converting enzyme inhibition: search for additional mechanisms of action. 302 9

The local effects of angiotensin II (ANG II) on the heart may play an important role for the pathophysiology of cardiovascular disease. Numerous in vitro studies have demonstrated that angiotensin II has distinctive cellular effects in the cardiovascular system which are independent from its effects on blood pressure. These have led to the hypothesis that activation of the angiotensin system in the heart could be of functional relevance for the adaptive processes in several cardiovascular disorders such as cardiac hypertrophy heart failure. This concept has been further supported by clinical studies showing the beneficial effects of angiotensin-converting enzyme inhibitors in these circumstances. In order to study the gene regulation of renin-angiotensin system components in cardiac disorders we investigated the gene expression of angiotensin converting enzyme in human heart failure. Results showed that the enzyme is activated locally in this condition, supporting previous studies in animals. Taken together with recent evidence from genetic studies linking the enzyme to myocardial infarction and cardiac hypertrophy, our findings are in support of the notion that angiotensin converting enzyme plays a central role in cardiovascular physiology and pathophysiology.
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PMID:Role of the cardiac renin-angiotensin system in human heart failure. 748 29

Molecular genetics is playing an increasing role in the diagnosis, treatment, and prevention of cardiac disease. Moreover, most of the genes that may cause cardiac disease or predispose an individual to cardiac disease are anticipated to be identified within the next 10 years. Several genes with risk for heart disease have been identified, such as the ACE genotype DD. Replacement gene therapy as well as use of promoter-specific drugs to act on genetic regulatory elements will encompass the future treatment of cardiovascular disease. This article provides a summary of the potential roles of genetic screening for cardiac risk factors and genetic interventions in cardiovascular disease.
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PMID:Molecular genetics: cardiac disease and risk-related genes. 748 15

The effects of cardiovascular drugs on endothelium and vascular smooth muscle function are important for the prevention of cardiovascular disease. Changes in endothelial function are an early event in most forms of cardiovascular disease and, later in the disease process, vascular smooth muscle cells are functionally altered and begin to migrate to and proliferate in the intima. Calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are widely used in patients with cardiovascular disease and are thought to have vascular protective effects. ACE, an enzyme located in the endothelial cell membrane, activates angiotensin I and angiotensin II, and deactivates bradykinin. Bradykinin activates endothelial bradykinin (B2) receptors, which results in the formation of nitric oxide and prostacyclin. Hence, ACE inhibitors not only prevent the formation of angiotensin II, but also increase the local levels of bradykinin and in turn nitric oxide and prostacyclin. These compounds are vasodilators and potent inhibitors of platelet function, and therefore may mediate important protective effects of ACE inhibitors. Furthermore, nitric oxide may have antiproliferative effects in vascular smooth muscle cells. Calcium antagonists do not appear to affect the release of endothelium-derived relaxing factors or any other endothelial product. However, they facilitate endothelium-dependent relaxation and reduce the contracting effects of endothelin-1 at the level of smooth muscle. Indeed, in some blood vessels, e.g. the large coronary arteries and the human forearm circulation, verapamil and nifedipine antagonise endothelin-induced contractions. In addition, calcium antagonists inhibit the effects of platelet-derived growth factor and may have antiproliferative effects in vascular smooth muscle cells. In conditions involving progressive dysfunction of the endothelium, vascular deposition of platelets increases the local levels of platelet-derived growth factor, and the antiproliferative effects of calcium antagonists may thus be particularly important.
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PMID:Calcium antagonists and ACE inhibitors. Effect on endothelium and vascular smooth muscle. 751 65

It is well known that, in patients with essential hypertension, left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular disease. However, it has been demonstrated that normalisation of arterial pressure, by therapy with antihypertensive drugs, is associated with regression of LVH, although the extent and time-course of this phenomenon depend on the antihypertensive drug used. In particular, angiotensin converting enzyme (ACE) inhibitors seem capable of inducing a faster and more complete reversal of LVH in patients with essential hypertension than other antihypertensive drugs. The mechanisms underlying this property of ACE inhibitors remain unclear, although 2 features of ACE inhibitors may be particularly relevant. The first is their ability to improve large artery compliance, this being a major determinant of LVH. Arterial compliance is reduced in essential hypertension, resulting in increased left ventricular end-systolic stress, which then contributes to the development of LVH. The second possible mechanism by which ACE inhibitors reverse LVH to a greater degree than other antihypertensive drugs may relate to their ability to interfere with the cardiopulmonary receptor control of the circulation. Thus, ACE inhibitors may counteract the neural and hormonal abnormalities that contribute to the maintenance of LVH in hypertensive patients.
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PMID:Effects of angiotensin converting enzyme inhibitors on left ventricular hypertrophy. 751 89

Nitric oxide (NO), derived from the vascular endothelium and other cells of the cardiovascular system, has important roles in physiological regulation of blood flow and may have pathophysiological functions in cardiovascular disease. The mechanisms involved in NO-induced vasodilatation and cytotoxicity are briefly reviewed in the context of inflammatory reactions and cardiovascular function. Although NO can hyperpolarize vascular smooth muscle, activation of the endothelium can induce hyperpolarization and vasodilatation by other means. Endogenous inhibitors of NO generated by leucocytes may compromise blood flow distribution after ischaemia and reperfusion injury. Chronic heart failure is associated simultaneously with impairment of endothelium-dependent vasodilatation and with excess production of NO via the inducible NO synthase (iNOS), although it is unclear whether the latter ameliorates or exacerbates ventricular dysfunction. Excess NO production is also one of the earliest signs of transplant rejection, and suppression of iNOS expression by immunosuppressant drugs such as cyclosporin A might be one means by which these drugs protect allografts. Disturbances in the activity of NOS isoforms in the artery wall also accompany the development of atherosclerosis, providing conditions propitious for vasospasm and thrombosis. Reversing the NO defects with therapeutic agents, including angiotensin converting enzyme (ACE) inhibitors, offers promise in protecting against some manifestations of vascular disease.
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PMID:Endogenous nitric oxide in cardiovascular disease and transplantation. 754 30

This study was performed to investigate the beneficial effects of prolonged treatment with an angiotensin converting enzyme (ACE) inhibitor, delapril, on the appearance of symptoms of hypertensive cardiovascular disease in stroke-prone spontaneously hypertensive rats (SHRSP). Cardiovascular disease symptoms: stroke, kidney dysfunction and cardiac hypertrophy, were evaluated by monitoring the incidence of stroke signs, urinary excretion of protein and the heart weight, respectively. The SHRSP that were kept under salt-loaded conditions (1% NaCl drinking solution) from six weeks of age developed severe hypertension, showed an increased incidence of stroke signs and increased urinary excretion of protein. Long-term treatment with delapril (10mg/kg/day, p.o. for four weeks) decreased the blood pressure and completely inhibited the incidence of stroke signs and the increase in urinary excretion of protein. In SHRSP that were kept under normal conditions (without 1% NaCl drinking solution), long term treatment with delapril at the same dose decreased the heart weight and, after five weeks of treatment, left ventricular weight was decreased significantly and the wall/lumen ratio of small coronary arterioles and the thickness of the left ventricular wall were decreased slightly. These results indicate that delapril can prevent the development of symptoms of hypertensive cardiovascular diseases: stroke, kidney dysfunction and cardiac hypertrophy, with antihypertensive activity in SHRSP.
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PMID:Effects of delapril on stroke, kidney dysfunction and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats. 755 8


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