Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

During ischaemia, both the circulating renin-angiotensin system and the local angiontensin converting enzyme are activated. The circulating renin-angiotensin system has a short-term role in the regulation of the cardiovascular system. Its aim is to restore blood pressure and cardiac homeostasis. Activation of the local system causes long-term regulation of cardiovascular homeostasis via sustained activation of local angiotensin and the gradation of bradykinin. This results in the secondary permanent structural changes that underline many aspects of coronary artery disease. Recently it has been shown that ACE inhibition is useful in the early and late phase of myocardial infarction. ACE inhibitors have been shown to reduce in vitro vascular hypertrophy and attenuate arteriolosclerosis and to maintain endothelial function. Interestingly, unexpected data from trials on heart failure have shown that patients receiving ACE inhibitors have a reduced incidence of infarction, hospitalization for cardiovascular disease and the need for coronary artery bypass surgery or angioplasty. As a consequence, several trials have been designed to assess the effect of ACE inhibition on the progression of coronary artery disease, as well as on its morbidity and mortality. The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) is one of these. This article summarised a number of independent and complementary mechanisms and points to the role played by ACE and ACE inhibition in coronary artery disease. In particular it considers the possibility that ACE inhibition improves endothelial function, exerts anti-atherogenic and anti-proliferation activity and modulates sympathetic activity.
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PMID:Effect of ACE inhibition on myocardial ischaemia. 979 38

Hypertension is an important risk factor for cardiovascular disease (CVD) in patients with normal renal function. After reviewing over two decades of clinical trial data and an even longer history of epidemiologic data, multiple consensus panels worldwide have made recommendations for the aggressive treatment of hypertension using both lifestyle modification and drug therapy. These data and recommendations provide the basis of the recommendations for preventing CVD in patients with renal disease. Most patients should have elevated blood pressure (BP) lowered to less than 140 mm Hg systolic and less than 90 mm Hg diastolic. Earlier and more aggressive intervention is recommended in high-risk hypertensive patients with risk factors (especially diabetes mellitus) or evidence of target organ damage or clinical CVD. Lifestyle changes are indicated as either initial therapy or concomitant therapy in all hypertensive patients to lower BP and to normalize other CVD risk factors. There is general agreement that clinical outcome data from controlled clinical trials should guide the selection of antihypertensive agents. Currently, these data are only available for thiazide diuretics and beta-blockers for most hypertensive patients with normal renal function and for the dihydropyridine calcium channel blockers in older hypertensive patients with isolated systolic hypertension. However, data may support the use of other agents in hypertensives with selected comorbidity (eg, ACE inhibitors in heart failure, beta-blockers after myocardial infarction, and so forth). However, with only 25% of hypertensive patients controlled to less than 140/90 mm Hg, achieving blood pressure control remains the most important goal in managing hypertension in this population.
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PMID:Prevention of cardiovascular disease in hypertensive patients with normal renal function. 982 Apr 66

Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans.
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PMID:Endothelin: role in hypertension. 983 May 7

Coronary heart disease and other vascular diseases account for approximately half of all deaths in women. Although the underlying pathophysiological processes (atherosclerosis and thrombosis) are similar, deaths and other clinical end-points are significantly delayed compared to men. The reason for this sex-related delay in the expression of vascular disease remains a matter of debate but may be largely attributable to the actions of endogenous oestrogens: coronary heart disease manifestations are extremely rare in premenopausal women but increase after the menopause. These observations have lead to speculation that oestrogen-replacement therapy might continue to retard the development of cardiovascular disease in the post-menopausal years (primary prevention). The cardioprotective benefits of oestrogens include a favourable impact on plasma lipids, anti-platelet effects, preservation of endothelium-mediated vasodilatation and antioxidant effects. Several observational studies support this thesis but the results of prospective randomised controlled trials are still awaited. Secondary preventative measures such as aspirin, beta-blockade, ACE inhibition and HMG-CoA reductase inhibitors seem to be equally effective for women as men. However, there remains evidence that physicians are less likely to use such interventions in women at high risk.
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PMID:Women and heart disease. 983 68

The increased risk of cardiovascular disease in diabetic patients is well documented. A greater appreciation for the importance of this fact and regular use of secondary prevention strategies, including aggressive use of HMG-CoA reductase inhibitors or other lipid-lowering agents to reduce cholesterol levels, are clearly indicated for diabetic patients with CAD. If no contraindications exist, ACE inhibitors, beta blockers, and aspirin also should be considered for these high-risk patients.
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PMID:Coronary artery disease and diabetes. 1002 4

Of the active fragments studied to-date, Ang-(l-7) is the most pleiotropic of the Ang I metabolities because it exerts effects that may be identical or opposite to those of Ang II. While much research remains to be done, accumulating evidence suggests that Ang-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, augments the metabolic actions of bradykinin, and increases the release of nitric oxide. This explains why Ang-(1-7) activates antihypertensive mechanisms, particularly in situations of increased Ang II activity. In other words, Ang-(1-7) may act as a negative feedback hormone of the pressor and trophic actions of Ang II. The enzymes forming Ang-( 1-7) reinforce the idea that this peptide is a component of a vasodepressor system that regulates blood pressure. Both neprilysin and metalloendopeptidase 24.15 form Ang-(1-7) but also cleave bradykinin and atrial natriuretic peptide to smaller fragments. Our recent discovery that Ang-(1-7) is a major substrate for angiotensin converting enzyme (ACE) adds a new and important dimension to the understanding of the biochemical physiology of the renin angiotensin system. Moreover, these data explain why Ang-(1-7) augmentes the hypotensive effects of bradykinin and contributes to the antihypertensive actions of ACE inhibitors. While the bulk of the research in hypertension continues to emphasize the investigation of the cellular actions of Ang II, our research has introduced new concepts and uncovered new mechanisms through which angiotensin peptides control homeostasis and influence the pathogenesis of cardiovascular disease.
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PMID:Angiotension-(1-7) and antihypertensive mechanisms. 1004 92

Both isolated systolic hypertension (>140 mm Hg/<90 mm Hg) and systolic/diastolic hypertension (>140 mm Hg/>90 mm Hg) are major risk factors for cardiovascular disease in the elderly. Specific antihypertensive drug therapy is available if lifestyle interventions fail to reduce blood pressure to a normal level. Diuretics and beta blockers both reduce the occurrence of adverse events related to cerebrovascular disease; however, diuretics are more effective in reducing events related to coronary heart disease. Treated patients are less likely to develop severe hypertension or congestive heart failure. In most instances, low-dose diuretic therapy should be used as initial antihypertensive therapy in the elderly. A long-acting dihydropyridine calcium channel blocker may be used as alternative therapy in elderly patients with isolated systolic hypertension. Trials are being conducted to evaluate the long-term effects of angiotensin converting enzyme inhibitors and angiotensin-II receptor blockers in elderly patients with uncomplicated hypertension.
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PMID:Hypertension treatment and the prevention of coronary heart disease in the elderly. 1050 42

Morbidity and mortality in diabetes are caused mainly by its vascular complications, both in the microcirculation and in the large vessels. Diabetic nephropathy and retinopathy are the clinical hallmarks of microangiopathy, which may lead to end-stage renal failure and blindness. The cardiovascular complications in diabetes consist mainly of an accelerated form of atherosclerosis. Systemic hypertension is an early and frequent phenomenon. Nocturnal hypertension is also more frequent in people with diabetes compared with the nondiabetic population. Capillary hypertension has been demonstrated in type 1 diabetic patients. Poor metabolic control may induce elevation in blood pressure, but data are conflicting. The prevalence of white-coat hypertension in the diabetic population is comparable with that in the nondiabetic population. Prospective observational studies in type 1 and type 2 patients have revealed that abnormally increased urinary albumin excretion and other potentially modifiable risk factors--such as hypertension, smoking, poor metabolic control, and social class--predict increased all-cause mortality and cardiovascular mortality. Arterial hypertension is a risk factor in the initiation and progression of diabetic micro- and macroangiopathy. Diabetes, hypertension, and smoking are the three most important risk factors for fatal and nonfatal stroke. A randomized, double-blind, parallel study has revealed that the 5-year major cardiovascular disease rate was lowered by 34% for antihypertensive treatment compared with placebo. Furthermore, the study found a trend for lower all-cause mortality for low-dose antihypertensive-treated diabetic patients. Effective blood pressure reduction with ACE inhibitors and/or non-ACE inhibitors, frequently in combination with diuretics, reduces albuminuria, delays the progression of nephropathy, postpones end-stage renal failure, and improves survival in diabetic nephropathy.
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PMID:Diabetic hypertensive patients. Is this a group in need of particular care and attention? 1009 4

Cardiovascular disease is a leading cause of death in diabetic patients. It has been reported to count for almost 80% of all deaths. About three-fourths of these deaths result from coronary artery disease. Studies have shown that diabetic patients who have had an acute myocardial infarction (AMI) have a mortality of about twice that of nondiabetic patients. Various medications have been shown to improve the prognosis among diabetic patients suffering from ischemic heart disease. They include beta-blockers, thrombolytic agents, aspirin, ACE inhibitors, and lipid-lowering drugs. Experiences indicate that treatment with beta-blockers, thrombolytic agents, and ACE inhibitors is particularly advantageous in diabetic patients who have suffered AMI. Metabolic control also may be of major importance during the acute cardiac event because it is assumed that fatty acid metabolism is increased with a compromised glycolysis not only in ischemic but also in the nonischemic areas. One way to suppress free fatty acid oxidation is by the infusion of insulin-glucose. In the Swedish Diabetes Mellitus and Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study, patients with diabetes and AMI were randomized to receive insulin-glucose infusion followed by intensive subcutaneous insulin treatment or to be control subjects. The 1-year mortality was reduced 30% by insulin treatment. Diabetic patients who suffer from coronary artery disease have a particularly adverse prognosis. Previous experiences indicate that treatment with beta-blockers, thrombolytic agents, and ACE inhibitors is particularly advantageous in diabetic patients who have suffered AMI. Aspirin and lipid-lowering drugs should be offered to these patients on traditional indications as well. Metabolic control seems to be of major importance for the outcome.
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PMID:How to improve the cardiac prognosis for diabetes. 1009 7

Calcium antagonists continue to have a place in the treatment of hypertension, despite recent concerns regarding their safety and long-term capacity to alter the natural history of cardiovascular disease. Results of a well-designed cohort study concerning a very elderly population suggested that administration of shorft-acting nifedipine is linked to an increase in mortality, particularly when a high dose is administered and when the initiaol blood pressure is below 160/90 mmHg. The risk of using short-acting verapamil, however, was no greater than that of beta-blockade. These differences can be attributed at least in part to the low catecholamine profile of verapamil and to the marked rapid adrenergic activation with short-acting nifedipine. Current evidence sujggests that less catecholamine activation occurs during the chronic use of long-acting dihydropyridine agents. Two recent studies have shown that the combination of verapamil and an angiotensin converting enzyme inhibitor reduces numbers of cardiovascular disease events among postinfarct patients with heart failure, and that the dihydropyridine nitrendipine reduces poor outcome measures, such as stroke incidence, in treating systolic hypertension in the elderly. In my view, apparent hazards such as the precipitation of myocardial infarction and cancer are discounted by the available evidence. While we await further major trials concerning outcomes, general safety can be related to a preference for administering those long-acting agents that do not stimulate and may even inhibit adrenergic responses, and the avoidance of possible adverse effects through the use of combination therapies, such as verapamil plus an angiotensin converting enzyme inhibitor or nifedipine plus a beta-blocker.
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PMID:Ongoing clinical outcome studies of calcium antagonists. 1021 33


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