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)

Based on studies in the rat remnant kidney model, it has been proposed that glomerular hypertension is responsible for the progressive nature of chronic renal disease. In that model, therapy with angiotensin converting enzyme (ACE) inhibitors reduced glomerular pressures. As a result, glomerular injury was reduced and the rate of progression of renal disease was slowed. Thus, alterations in hemodynamics may play an important role in glomerular injury. However, it is now evident that a variety of metabolic and other factors affect the progression of renal disease. Moreover, recent studies suggest that ACE inhibitors may also have beneficial effects that are independent of alterations in glomerular pressure. In humans, the glomerular hemodynamic response to renal disease cannot be measured, and it is not known whether or under which conditions glomerular capillary pressure might be elevated. Treatment with ACE inhibitors safely lowers blood pressure without adversely affecting renal function in most patients with nondiabetic chronic renal failure. Although proteinuria and the rate of progression of renal disease may decrease in some patients, these effects are inconsistently seen. Identification of the factors that modulate this variability in response to ACE inhibition may provide new insight into the pathogenesis and treatment of progressive renal disease in humans.
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PMID:Renal effects of angiotensin converting enzyme inhibitors: nondiabetic chronic renal disease. 228 14

1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure. 252 41

To determine whether pharmacological control of blood pressure could affect the renal function and levels of atrial natriuretic polypeptide (ANP) in spontaneously hypertensive rats (SHR) with renal ablation, and to ascertain the benefits of antihypertensive drugs, we studied effects of oral administration of captopril (50 mg/kg/day), an inhibitor of angiotensin converting enzyme, benidipine (3 mg/kg/day) and nilvadipine (10 mg/kg/day), newly developed blockers of calcium channel, and indapamide (10 mg/kg/day) for 14 days on systolic blood pressure, serum creatinine, blood urea nitrogen, and plasma ANP concentration in SHR subjected to surgical removal of the left kidney and infarction of two-thirds of the right kidney (5/6 nephrectomy) a week before. Three weeks after the surgery, systolic blood pressure (mmHg) in the untreated group was 253 +/- 9 (n = 10), in the captopril group 156 +/- 9 (n = 7, p less than 0.05), in the benidipine group 197 +/- 9 (n = 7, p less than 0.05), in the nilvadipine group 146 +/- 9 (n = 7, p less than 0.05) and in the indapamide group 206 +/- 5 (n = 7, p less than 0.05). Serum creatinine (mg/100 ml) was lower in the captopril group (0.58 +/- 0.02, n = 7, p less than 0.05) and in the benidipine group (0.50 +/- 0.03, n = 7, p less than 0.05) but not in the nilvadipine group and in the indapamide group 3 weeks after 5/6 nephrectomy compared to the untreated group. Blood urea nitrogen was also lower in the captopril group and in the benidipine group but not in the nilvadipine group and in the indapamide group. Plasma ANP concentration was significantly reduced by the treatment with captopril and benidipine but not with nilvadipine and indapamide. These results suggest that the reduction of blood pressure by the inhibition of angiotensin converting enzyme with captopril has the potential to ameliorate renal function of the SHR with remnant kidney, a model of chronic renal failure with hypertension, associated with the decreased concentration of plasma ANP. However, it remains to be determined whether the reduction of blood pressure by calcium channel blockers may be involved in the delayed progression of renal failure in this model since there were disparate effects on renal function and plasma ANP concentration with these two calcium channel blockers.
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PMID:Effects of antihypertensive drugs on renal function and atrial natriuretic polypeptide in spontaneously hypertensive rats with renal ablation. 252 46

1. We have investigated the effects of the non-renin-mediated actions of angiotensin converting enzyme inhibitors on the progression of chronic renal failure accelerated by hypertension. For this purpose, we studied the effects of captopril (a thiol-containing angiotensin converting enzyme inhibitor), enalapril (an angiotensin converting enzyme inhibitor without a thiol group) and cysteine (a thiol-containing amino acid which has no angiotensin converting enzyme-inhibitory action) in adriamycin-treated rats with deoxycorticosterone acetate-salt hypertension, in which the renin-angiotensin system was suppressed. 2. There were no significant differences in blood pressure between these groups and the control group [adriamycin-treated group with deoxycorticosterone acetate-salt loading, 206 +/- 7 mmHg (27.4 +/- 0.9 kPa) at week 10]. 3. Massive proteinuria occurred in all groups. At the end of the experiment (at week 10), urinary protein excretion was significantly reduced in the captopril and cysteine groups compared with the control group. No manifest improvements appeared in the enalapril group. 4. Levels of serum creatinine and blood urea nitrogen increased progressively. At week 10, the increases in the serum levels of creatinine were less in the captopril (87 +/- 16 mmol/l) and cysteine (80 +/- 19 mmol/l) groups than in the control group (124 +/- 27 mmol/l) (P less than 0.01). No marked differences were found between the control and enalapril groups. 5. Captopril and cysteine caused more than a three-fold reduction in the focal glomerulosclerosis score when compared with that in the control group, but enalapril did not decrease the score. The extent of tubulointerstitial change was parallel with the focal glomerulosclerosis score. 6. We conclude that the thiol group is possibly involved in the mechanism of the beneficial effects of some angiotensin converting enzyme inhibitors on the progression of chronic renal failure exacerbated by hypertension.
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PMID:Differences in the effects of angiotensin converting enzyme inhibitors with or without a thiol group in chronic renal failure in rats. 254 Sep 31

Since the introduction of angiotensin converting enzyme (ACE) inhibitors into clinical use, much information has been accumulated in animal models and man regarding their effects on renal function in different disease states. Enalapril, the first nonsulfhydryl ACE inhibitor approved for general use in the United States, has demonstrated efficacy and safety in controlling blood pressure in patients with essential hypertension, renal parenchymal disease, renovascular hypertension, and diabetes with hypertension. Enalapril also appears capable of attenuating the progressive nature of renal disease in experimental models of chronic renal failure and diabetic nephropathy, perhaps through lowering intraglomerular pressures. The excellent blood pressure-lowering effects of ACE inhibitors, coupled with their potential to ameliorate renal hemodynamic abnormalities, make these compounds attractive for use in these clinical states.
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PMID:The effects of enalapril on blood pressure, renal hemodynamics, and renal function. 255 60

We studied the long-term effect of an angiotensin converting enzyme (ACE) inhibitor, captopril, on the progression of chronic renal failure and on the rate of urinary protein excretion. When compared with standard triple therapy, captopril slowed the progression of renal failure. Captopril was also able to reduce the proteinuria of non-diabetic glomerular origin. This reduction was not dependent on the presence or absence of arterial hypertension but was limited by the presence of low serum albumin levels, and only occurred in patients with proteinuria in excess of 3 g/24 h.
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PMID:Effects of angiotensin converting enzyme inhibitors on the progression of renal failure and proteinuria in humans. 269 57

Camostat mesilate, a developed derivative of gabexate mesilate for oral use, was administered in a daily dose of 600 mg for 4 weeks to 17 patients with heavy proteinuria due to various nephropathies. Five patients had glomerulonephritis (3 patients with IgA nephropathy, one each with membranoproliferative GN and membranous nephropathy) and 3 had systemic vasculitis. These patients had been treated with glucocorticoid, cyclophosphamide, anticoagulants, and dipyridamole. Five patients had diabetic nephropathy and had been treated with conventional therapy including angiotensin converting enzyme inhibitors. Two cases with benign nephrosclerosis, one with Alport syndrome, and the rest with end-stage renal failure of undetermined cause were also included in this study. Urinary protein decreased promptly within 2 weeks (from 5.2 +/- 0.7 to 3.5 +/- 0.5, mean +/- SE, p less than 0.005), and serum total protein and albumin levels increased significantly. Serum creatinine levels did not change. Decreases in urinary protein excretion of more than 50% were observed in five out of eight patients with glomerulonephritis or systemic vasculitis, two out of five with diabetic nephropathy, and one with chronic renal failure. However, urinary protein excretion values remained at the same level in two patients with benign nephrosclerosis and a patient with Alport syndrome. We suggest that camostat mesilate caused a change in glomerular capillary permeability for macromolecules through its inhibitory effects on the kallikrein-kinin system, complement system, coagulation system, and platelet function, which contributed to the treatment of the various nephropathies.
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PMID:Effect of camostat mesilate on heavy proteinuria in various nephropathies. 279 62

The aim of this study was to evaluate the changes of ACE levels during RAAs activation induced by: 1) a continuous graded bicycle ergometer test performed in a group of 15 males health youths aged between 21 and 30 years, with average age of 25.8 +/- 2.85 years; 2) i.m. injection of 20 mg of frusemide in 11 health youths (10 males and 1 female), aged between 20 and 30 years, with average age of 24.09 +/- 2.77 years; 3) dialytic treatment in 25 patients (12 males and 13 females), suffering from chronic renal failure, aged between 26 and 68 years, with average age of 54 +/- 15.42 years. Plasmatic renin activity (PRA), aldosterone (ALD) and ACE levels were determined by RIA in basal conditions and at peak of exercise in group 1, 15 minutes after i.m. injection of frusemide in group 2 and after a session of dialysis in group 3. In all the experimental conditions studied there was an activation of the renin-angiotensin system with significant increase of the PRA, ALD and ACE levels.
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PMID:Changes of angiotensin converting enzyme (ACE) levels during activation of the renin-angiotensin-aldosterone system (RAAs). 282 97

In order to establish if pharmacological treatment of systemic hypertension modifies the course of progressive renal failure, we studied the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist, on the renal structure and function in the remnant kidney model of chronic renal failure in the rat. Progressive renal failure was induced in adult female Sprague Dawley rats (SDR) by surgical removal of the right kidney, and segmental infarction of seven-eighths of the left kidney. Following subtotal nephrectomy, plasma creatinine rose from 65 +/- 16 mumol/l to 173 +/- 19 mumol/l (P less than 0.001) over a period of 6 weeks, systolic blood pressure (SBP) rose from 121 +/- 2 mmHg to 176 +/- 7 mmHg (P less than 0.001) and urinary protein excretion from 0.6 +/- 0.2 to 84 +/- 22 mg/24 h (P less than 0.001). Glomerular mesangial expansion was present after 2 weeks, then progressed, in association with the development of glomerular sclerosis, which became prominent after 6 weeks. Rats were treated with enalapril (5 mg/kg per day) or felodipine (30 mg/kg per day) from 1 week after subtotal nephrectomy, and their course compared with that of untreated rats. Systemic SBP decreased to a similar degree by both drug treatments. Six weeks after surgery, plasma creatinine concentration was lower in the enalapril-treated group (110 +/- 8 mumol/l, P less than 0.05) than in the felodipine-treated group (153 +/- 23 mumol/l). The latter group showed similar plasma creatinine concentrations to those of the untreated rats (173 +/- 19 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The contribution of systemic hypertension to progression of chronic renal failure in the rat remnant kidney: effect of treatment with an angiotensin converting enzyme inhibitor or a calcium inhibitor. 284 93

1. Lisinopril, a new orally active angiotensin converting enzyme inhibitor, was given to eight patients with stable chronic renal failure, in a dose of 5 mg 24 h-1 for 1 week. Creatinine clearance of the subjects ranged from 0.22 to 1.11 ml s-1. Lisinopril pharmacokinetics were studied over 8 days. 2. There was a close correlation between creatinine clearance and total 'area under the curve' over the 8 days of study (r = -0.88, P less than 0.05), and plateau lisinopril concentration and creatinine clearance (r = -0.77, P less than 0.05). 3. Serum angiotensin converting enzyme activity was inhibited in proportion to log serum lisinopril concentration (r = -0.99, P less than 0.001). Calculated IC50 was 47 ng lisinopril ml-1. from pooled data, with individual patients IC50 ranging from 20 to 70 ng lisinopril ml-1. 4. Creatinine clearance was unaltered by treatment. Serum potassium rose to over 5 mmol 1-1 in four patients, without adverse clinical effect.
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PMID:Lisinopril pharmacokinetics in chronic renal failure. 284 71


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