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)

An interim analysis of the AASK trial at three years demonstrates a renoprotective effect [slower decline in glomerular filtration rate (GFR), delayed onset of significant decrease in GFR, end-stage renal disease (ESRD) or death, and a decrease in urinary protein excretion] of the angiotensin converting enzyme (ACE) inhibitor, ramipril, as compared to the dihydropyridine calcium channel blocker (DHP-CCB), amlodipine, in patients with mild-to-moderate renal insufficiency. The beneficial effect occurred in the presence of similar levels of blood pressure control and was apparent in patients with proteinuric (beyond the threshold of "dipstick positive" proteinuria, 300 mg/day) and non-proteinuric hypertensive nephrosclerosis. At the time of the interim analysis, the effectiveness of the beta-blocker metoprolol was not significantly different from that of the ACE inhibitor. The data suggest that DHP-CCBs should be used with caution in the presence of mild-to-moderate renal insufficiency.
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PMID:ACE inhibition is effective and renoprotective in hypertensive nephrosclerosis: the African American Study of Kidney Disease and Hypertension (AASK) trial. 1286 79

Even well-conducted randomized controlled trials can only reduce uncertainty, not eliminate it. The trials presented in this article all have gaps, and like many studies, some raise more questions than answers. A summary of the current trials, however, can be presented as follows. For patients with essential hypertension who are at high risk for cardiovascular disease, the use of diuretic therapy (excluding simultaneous use of ACE or CCB) resulted in outcomes at least equivalent to the use of either ACE or CCB without diuretics. Naturally, the dilemma for clinicians is that these drugs are most often used in combination with thiazide diuretics, as indicated by the RENAAL trial where 80% of ARB were used with diuretics in patients with type II diabetes and known nephropathy. The increased risk of heart failure observed with ACE and CCB in that trial may be relevant only to patients in whom diuretics were not also used. The study does raise important awareness, however, that ACE or CCB use without diuretic therapy is no better than diuretic therapy, and may be associated with higher risk of certain outcomes. A substantial number of patients with essential hypertension might achieve adequate blood pressure control with diuretic monotherapy. If so, that certainly has important implications for the cost of medical care in this country. For African Americans with essential hypertension, ACE may have advantages as a component of therapy in comparison with CCBs or beta-blockers, although diuretics should probably be the cornerstone of therapy for them and supported by the Seventh Joint National Committee. For patients with proteinuric renal disease, whether associated with diabetes or hypertension, it should be considered inappropriate to use DHP CCB as monotherapy in any setting, whether as part of a clinical trial or in clinical practice. These drugs should not be considered as ethical placebo arms in trials, most especially in diabetic nephropathy, nor should they be used without an ACE or ARB in patients with proteinuric renal disease in the absence of documented contraindications or intolerance to ACE, ARB, or non-DHP CCB (which are now considered second-line agents for proteinuric renal disease, and are acceptable placebo or comparison arms in clinical trials). For patients with type I diabetes, ACE remain the cornerstone of therapy. Because of recent RENAAL and IDNT trial results, the greatest benefit for slowing progression of renal disease in type II diabetic nephropathy now belongs to ARBs. In contrast, however, the HOPE trial showed that ACE, specifically ramipril, had the greatest evidence for prevention of cardiovascular outcomes in patients with renal insufficiency, regardless of diabetic status. Cardiovascular outcomes were secondary end points in the RENAAL and IDNT trials, and with the exception of heart failure for losartan, no benefits on cardiovascular outcomes were statistically significant. Progression of renal disease has only been studied in a relatively small cohort of Israeli patients comparing enalapril with nifedipine. These gaps lead to a classic dilemma in medical decision-making. Because evidence has shown that patients with elevated serum creatinine (greater than or equal to 1.4 mg/dL) are just as likely to die from cardiovascular disease as they are to reach end-stage renal disease, which outcome should be the focus for clinicians, or for researchers? Using a strictly evidence-based approach, this question can only be answered by yet another large, long, randomized, controlled trial. Given the similarity of actions between the ARB and ACE, it is likely there is considerable overlap of both benefits and side-effects between the two, although ARB may have a lower incidence of cough and hyperkalemia. The decision of which antihypertensive agents to use will have to be tailored carefully to the needs of the patient and careful consideration of both medical and economic factors. Regardless of the choice between an ACE or ARB, however, post hoc analysis of clinical trials [21,47] and observational data clearly indicate that patients with chronic kidney disease, even if considered mild (ie, serum creatinine greater than or equal to 1.4 mg/dL) are at significantly greater risk of cardiovascular morbidity and mortality compared with those with better kidney function. As stated in a recent review by the authors of the HOPE trial [50], "the frequent practice of withholding ACE [or ARB] in patients with mild renal insufficiency is unwarranted," because not only are these patients precisely those who might benefit most from their use, but safety and tolerability are generally excellent. Based on the results of the AASK trial, the authors add the same for the use of ACE inhibitors in African Americans.
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PMID:What have we learned from the current trials? 1487 Oct 59

Our review of cohort studies and clinical trials evaluating antihypertensive drugs in the prevention of cognition decline and all dementia in patients with hypertension indicates that two antihypertensive drug classes have greater protective effects, independent of blood pressure decrease: dihydropyridine calcium-channel blockers as shown in the Syst-Eur trial and angiotensin-AT1 receptor blockers as found in the MOSES and ONTARGET trials. By contrast, diuretics and angiotensin-converting enzyme-inhibitors (ACEIs) prevent dementia only in patients with a stroke history, provided they are combined, and prevent stroke recurrence. A Japanese cohort study and a small trial in patients already suffering from Alzheimer's disease (AD) suggest, however, that the BBB-penetrating ACEI may slow down cognitive decline. Only cohort studies support the hypothesis that diuretics, (especially potassium-sparing diuretics), may decrease the risk of AD. beta-blockers worsen cognition decline, or are neutral, according to whether or not they cross the BBB. Centrally-acting sympatholytic agent have a negative impact on cognition as BBB-penetrating beta-blockers, probably by blunting the adrenergic pathways. The AD protective effect of DHP appears related to the blockade of neuronal calcium channels. The ambiguous effect of ACEI on cognitive decline and dementia prevention may be explained by the fact that brain ACE is not specific for angiotensin-I. Brain ACE also catabolizes cognition-enhancing brain peptides, amyloid peptides and converts toxic Abeta(42) into less toxic Abeta(40). Therefore, ACEIs may have short-term cognition-enhancing properties and may increase in the long term Abeta(42) brain burden and cognitive decline. The clinical relevance of this scenario, mainly observed in animals, cannot be excluded in man, since the ACE gene has been associated with AD via the human whole genome analysis. To support the hypothesized deleterious effect of ACEI on human AD, confirmation that the ACE gene polymorphism DD is associated with protection against AD is necessary, since this polymorphism increases ACE activity. Independently of their preventive impact on beta-amyloid degenerative neuropathological process by overexpressing insulin degrading enzyme which catabolyses amyloid, the angiotensin AT1-receptor-blockers may have greater cognition protective effects than ACEI (observed in the ONTARGET trial), as they share with ACEI cognition-enhancing effects directly linked with a common AT1-blunting effect. In addition, they increase angiotensin II and IV formation and therefore stimulate non-opposed AT2 and AT4 receptors, whose activation in cognitive processes is well established.
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PMID:Prevention of dementia by antihypertensive drugs: how AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors. 1976 54

Four polysaccharides from Dendrobium huoshanense (DHP), D. officinale (DOP), D. nobile (DNP) and D. chrysotoxum (DCP), which had obvious differences in intrinsic viscosities and monosaccharide compositions, were extracted to compare their hypoglycemic and antioxidative activities in alloxan-induced diabetic mice by oral administration. The analysis of fasting blood glucose, glycosylated serum protein and serum insulin levels showed that DHP, DOP and DNP, but not DCP, possessed significant hypoglycemic effect with the decreasing order of DHP>DNP>DOP. Histopathological observation confirmed the capability of DHP, DOP and DNP to intervene the damage in pancreas tissues. The determination of superoxide dismutase, catalase, malonaldehyde and L-glutathione levels in the liver and kidney displayed that DHP, DOP and DNP had protective effects against alloxan-induced oxidative damage and the effect of DHP ranked first. These results suggested that there were significant differences in hypoglycemic and antioxidative activities between four Dendrobium polysaccharides, which may be contributed to their physicochemical properties.
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PMID:Comparison of hypoglycemic and antioxidative effects of polysaccharides from four different Dendrobium species. 2437 Apr 75