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)

Previous studies have shown that glucose increases angiotensin II (AngII) levels in rat glomerular mesangial cells and that AngII mediates the inhibitory effects of high glucose on matrix degradation in these cells. The present study addresses the following questions: (1) What are the mechanisms for the generation of AngII in mesangial cells? (2) What are the effects of glucose on AngII generation by these mechanisms? Experiments employed primary mesangial cells from normal Sprague-Dawley rats. The levels of immunoreactive angiotensinogen (AGT), angiotensin I (AngI), and angiotensin II (AngII) were measured by ELISA. AGT mRNA expression was determined by Northern blot analysis. Incubation of cells for 24 h in high glucose (30 mM) increased AGT levels by 1.5-fold and increased AGT mRNA expression; this was accompanied by a 1.5-fold increment in AngI and 1.7-fold increment in AngII levels. Renin activity (measured as AngI generation in the presence of excess AGT) and ACE levels and activity were not altered by high glucose. In further experiments, the effect of high glucose on formation of Ang peptides from exogenous AngI in mesangial cell extracts was examined using HPLC. Exogenous AngI was converted into various Ang peptides, including AngII, Ang(1-9), Ang(1-7), and Ang(3-8). A significant increase in formation of AngII from AngI was observed in cells incubated in high glucose. In addition, AngII production from exogenous Ang(1-9) in cell extracts was also stimulated by high glucose. These findings demonstrate that glucose increases mesangial AngII levels via an increase in AGT and AngI. In addition, this study provides new information that Ang(1-9) is produced by mesangial cells, can be converted to AngII, and that this conversion is also stimulated under high-glucose conditions.
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PMID:Mechanism of increased angiotensin II levels in glomerular mesangial cells cultured in high glucose. 1266 Mar 21

The prevalence of congestive heart failure (CHF) doubles with each decade after the fourth decade. CHF is associated with significant mortality and morbidity. Renin-angiotensin-aldosterone and sympathetic nervous systems play a pivotal role in the progression and deterioration of CHF. Multiple, double-blinded, randomized and placebo-controlled trials have shown significant survival benefit and improved quality of life with the use of neurohormonal antagonists, viz. angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor type 1 blockers, beta-blockers and spironolactone in the management of CHF. While important for the symptom control, diuretics and digoxin are not associated with any decrease in mortality in patients with CHF. Despite overwhelming evidence of decreased mortality and morbidity, neurohormonal antagonists remain under-utilized in the management of CHF. This article will review the current evidence for the survival benefit with the use of neurohormonal antagonists in CHF.
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PMID:Evidence for the survival benefit of neurohormonal antagonists in the management of geriatric congestive heart failure. 1268 26

Several clinical trials have consistently shown that antihypertensive treatment, particularly with angiotensin-converting enzyme inhibitors (ACE-I) reduces albuminuria in Type 1 diabetic patients. More recently, data on the beneficial effects of ACE-I on the preservation of glomerular filtration rate and renal ultrastructure have emerged. However, in general, these trials have recruited a wide spectrum of diabetics, including some patients with severe albuminuria. Thus, the question of the ideal stage at which to instigate what is likely to be lifelong therapy in young people still remains unanswered. Exercise is known to significantly increase both blood pressure (BP) and urinary albumin excretion (UAE), both of which are important determinants of progression of nephropathy in diabetes. Thus, it is possible that exercise may have an adverse effect on diabetic renal disease. The effects of ACE-I on exercise-BP and exercise-UAE in microalbuminuric Type 1 diabetic patients has not been examined in long-term placebo-controlled studies. In the second part of this two-part review, we examine the effects of the ACE-I, lisinopril, 20 mg o.d. for two years, in comparison with placebo, on UAE, 24-hour ambulatory BP, exercise-BP, exercise-UAE and renal haemodynamics in 22 patients with Type 1 diabetes and low-grade microalbuminuria. We further discuss the effects of ACE-I on nephropathy and other complications of diabetes.
J Renin Angiotensin Aldosterone Syst 2003 Mar
PMID:ACE inhibitor intervention in Type 1 diabetes with low grade microalbuminuria. 1269 49

Arterial Hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, activation of the Renin-Angiotensin-Aldosteron-System (RAAS), vasoconstriction, and microvascular rarefaction. The latter contributes to target organ damage, especially in left ventricular hypertrophy, and may partially be due to impaired angiogenesis. Angiogenesis, the formation of new microvessels and microvascular networks from existing ones, is a highly regulated process that arises in response to hypoxia and other stimuli and that relieves tissue ischemia. In AH, angiogenesis seems impaired. However, blood pressure alone does not affect angiogenesis, and microvascular rarefaction is present in normotensive persons with a family history for AH. Normal or increased NO in several processes and diseases enables or enhances angiogenesis (e.g. in portal hypertension) and reduced NO biosynthesis (for example, in a rat model of AH, in other disease models in vivo, and in endothelial NO Synthase knock out mice) impairs angiogenesis. Angiogenic growth factors such as Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) induce NO and require NO to elicit an effect. Effector molecules and corresponding receptors of the RAAS either induce (Bradykinin, Angiotensin II) or perhaps inhibit angiogenesis. The pattern of Bradykinin- and Angiotensin II-receptor expression and the capacity to normalize NO biosynthesis may determine whether ACE-inhibitors, Angiotensin II-receptor antagonists and other substances affect angiogenesis. Reconstitution of a normally vascularized tissue by reversal of impaired angiogenesis with drugs such as ACE inhibitors and AT1 receptor antagonists may contribute to successful treatment of hypertension-associated target organ damage, e.g. left ventricular hypertrophy.
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PMID:Hypertension and angiogenesis. 1287 Dec 5

Renin angiotensin system in the genesis of hypertension was established long after Goldblatt's belief that the minute capillaries of the kidney regulate blood pressure and he also suggested kidney released a pressure substance which lead to rise of blood pressure. Guyton provided experimental and analytical data supporting the role of renal pressure natriuresis in the regulation of normal circulation and its function resulting in the pathogenesis of hypertension. Hady and Overbeck proposed that the blood pressure of volume expanded hypertension was raised by a circulating inhibitor of the Na+/K+ ATPase pump. Brenner et al proposed that hypertension may arise from a congenital reduction in the number of nephrons or in the filtration surface area per glomerulus, thereby limiting ability to excrete sodium, raising blood pressure. Renin angiotensin system can be interrupted at four sites by adrenergic blocker, renin inhibitor, angiotensin converting enzyme inhibitor and angiotensin receptor blocker. Non-modulation in the face of relatively high dietary sodium could explain the pathogenesis of sodium sensitive hypertension and provide a more targeted, rational therapy for its correction.
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PMID:Role of kidney in hypertension. 1296 47

Occlusion of the artery of organs results in ischaemia. The opening of occluded artery results in tissue lesion identified as reperfusion injury (RI). Renin-angiotensin system seems to be involved in the RI. In this study we assessed the effects of different doses of two inhibitors of angiotensin converting enzyme (captopril or enalapril) and an angiotensin receptor type 1 (AT1) receptor blocker (losartan) in the RI of the kidney of rats. Female rats of 200-250 g were anaesthetized and used for RI studies. Different doses of captopril (5, 20 and 80 mg/kg), enalapril (1, 4 and 16 mg/kg) and/or losartan (5, 10 and 20 mg/kg) were used (s.c.) 120 min prior to the initiation of RI. Kidneys were removed and checked histologically for the presence and the grading of ischaemic injury. Appropriate controls were used as well, RI produced lesions comparable with that of ischaemia. Different doses of captopril or enalapril prevented these lesions. This is suggestive of the involvement of renin-angiotensin system in the RI. Different doses of losartan failed to prevent RI lesions which suggest that the effect of captopril or enalapril are not mediated through the AT1 receptors. Further studies on the involvement of AT2 receptor or other independent mechanisms are suggested.
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PMID:The preventive effect of captopril or enalapril on reperfusion injury of the kidney of rats is independent of angiotensin II AT1 receptors. 1470 20

Left ventricular systolic dysfunction is associated with neurohormonal activation which contributes to progressive ventricular remodeling and worsening clinical heart failure. Renin-angiotensin-aldosterone and sympathetic nervous systems are activated, not only in patients with clinically overt heart failure, but also in patients with asymptomatic or minimally symptomatic left ventricular systolic dysfunction. Activation of the angiotensin and adrenergic systems produces deleterious effects on systemic and coronary hemodynamics, promotes myocyte hypertrophy and fibroblast growth, and myocyte necrosis and apoptosis. Thus, therapy of heart failure should consist of pharmacologic agents not only to relieve symptoms but also to prevent and attenuate ventricular remodeling and progressive heart failure, thereby improving prognosis. In patients who are symptomatic, ACE inhibitors along with digitalis and diuretics as initial therapy (triple therapy) have the greater potential to improve exercise tolerance and decrease the incidence of treatment failure compared with diuretics alone or a combination of diuretics and digitalis. Diuretics alone should not be considered for long-term therapy as plasma renin activity, angiotensin II, aldosterone, norepinephrine and vasopressin levels may increase. ACE inhibitors decrease mortality in patients with heart failure resulting from left ventricular systolic dysfunction. The results of presently available studies indicate that angiotensin II receptor blockers (ARBs) do not provide any advantage over ACE inhibitors regarding survival benefit but may be better tolerated. Long-term adrenergic inhibition with the use of ss-adrenoceptor antagonists added to ACE inhibitors is associated with attenuation of ventricular remodeling, improvement in ventricular function and clinical class and survival of patients with symptomatic systolic left ventricular failure. Thus, initial pharmacotherapy for systolic heart failure should consist of: maximal tolerated dosages of ACE inhibitors;ARBs if ACE inhibitors are not tolerated because of intractable cough or angioedema;adequate dosages of hydralazine and isosorbide dinitrate if ACE inhibitors or ARBs are not tolerated; relatively low dosages of digoxin (serum concentrations of < or = 1.0 ng/dl) if not contraindicated; and diuretics to relieve congestive symptoms. Addition of spironolactone to ACE inhibitors can result in a significant reduction in the risk of sudden death in patients with symptomatic severe heart failure. Myocardial infarction resulting from ischemic heart disease is the most common cause of systolic left ventricular failure and the therapeutic modalities with potential to reduce the risks of myocardial infraction, such as risk factor modification, adequate control of diabetes and hypertension, antiplatelet agents and lipid-lowering agents, should also be included in the initial therapy.
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PMID:Congestive heart failure: what should be the initial therapy and why? 1472 93

The renin-angiotensin system (RAS) is well recognized for its importance in regulation of BP, electrolyte balance and vascular growth. Pharmacological suppression of the RAS, through ACE inhibition and/or angiotensin receptor blockade, is a proven effective therapeutic approach to the treatment of a range of cardiovascular diseases. Renin is the enzyme that catalyzes the first and rate-limiting step of RAS, the cleavage of angiotensinogen to angiotensin I (A-I). A-I is then further converted by ACE to the biologically active vasoconstrictor, A-II. Interruption of the generation of A-II by renin inhibitors at this highly specific initial step of the cascade would be expected to have similar but not identical effects to those of the already well established RAS antagonists. Due to the lack of effective alternative enzyme pathways, blockade of A-II production may be more effective with renin inhibition than with ACE inhibition, and because of the high specificity of renin for only one substrate, namely angiotensinogen, adverse effects would be expected to be less frequent. It is currently unclear whether blockade of angiotensin II type 1 receptors (AT(1)), leaving other A-II receptors unblocked, is preferable to the reduction in plasma and tissue A-II levels achieved with either ACE or renin inhibition. The development of early peptidic and peptidomimetic renin inhibitors was hampered by problems with oral bioavailability and high costs of synthesis. However recent work has led to the synthesis of a potent non-peptidic inhibitor of renin, aliskiren, which has acceptable oral bioavailability. This renin inhibitor has been shown to effectively reduce A-II levels in normal volunteers and to lower BP in patients with mild to moderate hypertension. It appears likely that aliskiren is the first of a new class of agents that may prove useful in the management of patients with nephropathy, heart failure and atherosclerosis in addition to hypertension.
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PMID:Therapeutic potential of renin inhibitors in the management of cardiovascular disorders. 1472 59

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P 0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P 0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.
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PMID:Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. 1474 33

In patients without target organ damage, a pharmacological antihypertensive therapy can be initiated with a monotherapy or a low dose combination therapy. A monotherapy often suffices to control blood pressure in patients with mild hypertension (140-159 mmHg systolic or 90-99 mmHg diastolic). In order to select the blood pressure-lowering drug that is best suited for an individual, monotherapies should be sequentially rotated, because it cannot be predicted to which drug a patient will best respond. Early initiation of a combination therapy is a good alternative. Theoretically, almost any of the six commonly used groups of antihypertensive drugs (ACE-Inihibitors, Angiotensin II-Receptor Antagonists, Beta-blockers, Calcium antagonists, Diuretics and Alpha blockers) can be combined with each other. However, combinations of Thiazid diuretics with inhibitors of the Renin-Angiotensin-Aldosteron-System (Beta blockers, ACE-Inhibitors, Angiotensin II-Receptor blockers) have proven most useful.
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PMID:[Combination therapy versus monotherapy: which strategy is better?]. 1519 38


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