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)

Both angiotensin converting enzyme (ACE) inhibition and sodium-diuresis lower blood pressure in spontaneously hypertensive rats (SHR). The purpose of the present study was to examine whether long-term therapy with ramipril (RA, and ACE inhibitor) would lower blood pressure more effectively and without adverse reactions in combination with the loop diuretics piretanide (PI) or furosemide (FU). Groups of 15 SHR each were treated once daily for 3 weeks by gavage with 1 and 10 mg/kg RA, 2 and 4 mg/kg PI, and 8 and 16 mg/kg FU alone and with 1 mg/kg RA in combination with each of these diuretics at both the high and low doses. Sustained and marked ACE inhibition with 10 mg/kg RA normalized BP, but this was accompanied with slightly impaired kidney function as assessed by increases in both urea and creatinine. Low-dose diuretic therapy, producing little diuresis, or treatment with 1 mg/kg RA, producing less sustained ACE inhibition were less effective on blood pressure and scarcely altered serum solute levels, except 4 mg/kg PI, which produced slight reductions in Na+, K+, Mg2+, and PO4(3-). Combined treatment with the 1 mg/kg RA with either diuretic given at low or high dose was well tolerated at much improved reduction in blood pressure compared to their effects individually and without changes in serum solute concentrations and without hemoconcentration. Thus, combined treatment with low doses of loop diuretics and ACE inhibitors that permit partial recovery of serum ACE activity during the 24 h after dosing synergistically lowers blood pressure without adverse reactions associated with larger doses of either therapy alone.
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PMID:Loop diuretics combined with an ACE inhibitor for treatment of hypertension: a study with furosemide, piretanide, and ramipril in spontaneously hypertensive rats. 247 99

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

Malignant hypertension developed in an 18-year-old man whose primary hypertension had been diagnosed by chance. Standing blood pressure was 290/170 mmHg. Tests of renal function revealed high blood urea nitrogen and creatinine levels and low levels of both effective renal plasma flow and the glomerular filtration rate. Plasma renin activity and levels of angiotensin II and aldosterone were greatly elevated. Severe concentric left ventricular hypertrophy was noted. The patient received standard antihypertensive treatment with furosemide, propranolol, nifedipine, and prazosin, but his blood pressure did not decrease and there was no improvement in the clinical or biochemical measures. The patient was then given 20 mg of enalapril daily for one year. The inhibition of angiotensin converting enzyme immediately reduced blood pressure. Angiotensin II and aldosterone levels became normal, kidney function and hemodynamics improved, and echocardiograms revealed that the left ventricular hypertrophy had regressed. The results confirm the pathogenetic role of angiotensin II in the development of the malignant phase of hypertension.
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PMID:Treatment of malignant hypertension with an angiotensin converting enzyme inhibitor. 255 Jan 35

Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.
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PMID:Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat. 267 Jul 94

Renal hemodynamics in heart failure and the effects of angiotensin converting enzyme (ACE) inhibition on renal function are reviewed. The incidence of renal dysfunction in patients with congestive heart failure is relatively high; however, the incidence of progression of renal dysfunction during treatment with ACE inhibitors is low. The mild reduction in renal function initially observed represents the physiologic expression of blocking both the systemic and the intrarenal compensatory activities of the renin-angiotensin system. Despite small changes in blood urea nitrogen and serum creatinine noted following initiation of enalapril therapy in the two studies described, there was no further clinically significant increase in blood urea nitrogen and serum creatinine noted during continued treatment in the majority of patients, irrespective of baseline renal function. The use of enalapril as adjunctive therapy with digitalis and diuretics in patients with congestive heart failure, with appropriate adjustment of the dosages of these agents, may benefit many patients.
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PMID:Effect of angiotensin converting enzyme inhibition on renal function in the treatment of heart failure. 267 17

The renin inhibitor CGP 29,287 was administered continuously for 7 days (30 mg/kg per day, intraperitoneally, via osmotic minipumps) to normotensive marmosets fed a low-salt diet. As a control, another group of marmosets was given vehicle only. After 7 days of treatment, the mean arterial blood pressure of the CGP 29,287-treated marmosets was significantly lowered by about 23 mmHg. Plasma immunoreactive total and active renin were increased 10- and sevenfold, respectively, whereas plasma renin activity (PRA) was reduced by 95%. Plasma angiotensin II (Ang II) and aldosterone were also reduced (by 97 and 85%, respectively). Serum angiotensin converting enzyme activity was unchanged and there were no differences in plasma concentrations of electrolytes, urea or creatinine between CGP 29,287-treated and control marmosets. These results indicate that although renin release is markedly stimulated after continuous administration of a renin inhibitor for 7 days, the formation of Ang II and aldosterone, the active hormones of the renin-angiotensin system, is substantially reduced.
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PMID:Biochemical effects of prolonged renin inhibition in marmosets. 268 8

The effect of clonidine, on alpha 2-agonist and antihypertensive, on the progression of chronic renal disease was studied in rats subjected to partial nephrectomy. Treatments began four weeks after the removal of approximately 70% of renal mass. Clonidine was given once daily by gavage on an increasing dose schedule of 50 micrograms/kg for 4 weeks, followed by 100 micrograms/kg for 8 weeks and finally 200 micrograms/kg for 6 weeks. Measurements of renal functions were made at 4 week-intervals during treatment. After 18 weeks, clonidine-treated rats had lower levels of plasma urea nitrogen (P less than 0.05) and plasma creatinine (P less than 0.05). Urinary protein excretion rates were lower in clonidine-treated rats while receiving 100 micrograms/kg at 8 weeks (P less than 0.05) and 200 micrograms/kg at 18 weeks (P less than 0.05). At the end of the treatment period, anesthetized clonidine-treated rats had a numerically lower mean arterial pressure (p = 0.08), but no difference in the histological ranking of light microscopic lesions (P greater than 0.10). Based on the functional data, we conclude that clonidine retards the deterioration of renal function in this model of chronic renal disease. The lack of a consistent effect of clonidine on proteinuria and no reduction in the severity of morphological damage indicates that clonidine is less effective than previously reported treatment in this model with angiotensin converting enzyme inhibition. These differences in efficacy may be related to differences in intraglomerular hemodynamic alterations and could be an important consideration in the selection of therapies for individuals with hypertension and renal insufficiency.
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PMID:Effect of clonidine on the progression of chronic renal disease in partially nephrectomized rats. 282 94

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.
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PMID:Renal function in urinary schistosomiasis in the Natal Province of South Africa. 282 52

Angiotensin converting enzyme [EC 3.4.15.1] was shown to exist in two distinct forms in bovine seminal plasma. The higher molecular weight form of the enzyme (angiotensin convering enzyme I) was purified to homogeneity by Sephadex G-200 gel filtration, and DEAE-Sepharose, blue Sepharose, and concanavalin A-Sepharose column chromatography. Final recovery of the enzyme was 9.0. The molecular weight of the enzyme was estimated to be 8 x 10(5) by the gel filtration method. A value of 4.6 x 10(5) was obtained for the reduced and denatured enzyme by dodecylsulfate polyacrylamide gel electrophoresis. The Stokes' radius, diffusion coefficient, and intrinsic viscosity of the purified enzyme were determined to be 95 A, 2.3 x 10(-7) cm2/s, and 6.76 ml/g. The enzyme had a specific activity of 105.12 mumol/min/mg protein for hippurylhistidylleucine. The Km value for hippurylhistidylleucine was found to be 20 mM. Studies with EDTA suggest that metal ions which are tightly bound are required for its activity. The enzyme was inhibited by some heavy metal ions but did not required sulfhydryl groups for its activity. Trypsin treatment of the urea-denatured enzyme produced a catalytically active fragment with an Mr of 30,000. Chemical hydrolysis of the native enzyme did not produce any active fragment.
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PMID:Molecular and catalytic properties of angiotensin converting enzyme-I from bovine seminal plasma. 285 88


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