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)

Cortex of rat kidney was homogenized and fractions enriched in plasma membrane, endoplasmic reticulum or brush border were prepared by several techniques of differential centrifugation. The identity and homogeneity of the membrane fragments were investigated by assaying marker enzymes and by transmission and scanning electron microscopy. Kallikrein was present in both plasma-membrane- and endoplasmic-reticulum-enriched fractions isolated by two fractionation procedures. Kallikrein was highly concentrated in a plasma-membrane fraction but was absent from the brush-border membrane of proximal tubular cells. Cells of transplanted renal tumours of the rat, originating from the proximal tubule, had no kallikrein activity. Kininase activity, angiotensin I-converting enzyme (kininase II) and angiotensinase were found in a plasma-membrane-enriched fraction and especially in the fraction containing isolated brush border. It is suggested that after renal kallikrein is synthesized on endoplasmic reticulum, it is subsequently reoriented to a surface membrane for activation and release. Renal kallikrein may enter the tubular filtrate distal to the proximal tubules. The brush-border membrane of proximal tubule is the major site of inactivation of kinins and angiotensin II..
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PMID:Isolation of membrane-bound renal enzymes that metabolize kinins and angiotensins. 18 28

It has been suggested that intrarenal levels of angiotensin II may preferentially control efferent arteriolar resistance or may influence the glomerular filtration coefficient (Kf). To examine these possibilities, micropuncture and clearance experiments were performed on nine anesthetized dogs evaluating renal and glomerular hemodynamics before and during the administration of an angiotensin converting enzyme inhibitor (SQ20,881). During the micropuncture measurements, renal arterial pressure was reduced to range of 85 to 90 mm Hg in order to maximize renin secretion and intrarenal formation of angiotensin II. Also, this procedure minimizes potential errors in the determination of single nephron glomerular filtration rate (SNGFR) and of glomerular pressure when estimated by techniques that require complete blockade of proximal tubule fluid flow. During the administration of SQ20,881, a converting enzyme inhibitor (CEI), renal blood flow increased significantly by 13%, but GFR was not altered. There were no significant alterations in SNGFR, proximal tubule pressure, peritubular capillary pressure or estimated glomerular pressure. By using the micropressure measurements in combination with the whole kidney hemodynamic data, it was estimated that afferent resistance was reduced 23%. Although significant decreases in efferent resistance could not be documented, there was a tendency for this variable to decrease also. Neither Kf nor effective filtration pressure were altered significantly by CEI. These results do not support the contention that intrarenal effects of angiotensin II are exerted predominantly on the efferent arteriolar resistance segments; rather, they suggest that angiotensin may exert a modest tonic effect on both pre- and postglomerular resistance elements in the anesthetized hydropenic dog.
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PMID:Glomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog. 39 40

In the kidney, angiotensin I-converting enzyme (ACE) is present in the vascular endothelial cells and in the brush border of epithelial cells of the proximal tubule. In spite of this well-known distribution of ACE, little is known of its regulation. In order to elucidate the possible mechanisms of control for brush border ACE, the effects of dexamethasone (DM), (40 micrograms s.c. per day, for 7 days) and triiodothyronine (T3) 0.5 mg/kg s.c. per day, for 10 days) were investigated in male Wistar rats. Plasma and brush border ACE activities were measured by fluorimetry in the presence of an artificial substrate Cbz-Phe-His-Leu and brush border ACE was characterized with a binding assay using 3H-ramiprilat, a specific radiolabelled ACE inhibitor. DM elicited a significant decrease in plasma ACE activity (from 0.46 +/- 0.03 to 0.28 +/- 0.02 nmol His-Leu/min/mg protein) but did not alter enzyme activity in the brush border: 47.12 +/- 5.12 nmol His-Leu/min/mg protein (control, n = 6) and 47.78 +/- 5.63 (DM, n = 6). Administering T3 produced a marked increase in the brush border ACE activity (from 42.87 +/- 4.9 to 81.41 +/- 11.7 nmol His-Leu/min/mg protein). Similarly, the maximum number of 3H-ramiprilat-binding sites increased in the brush border, indicating a good correlation between ACE activity and the quantity of 3H-ramiprilat bound. Thus, the variation in tissue ACE activity corresponded to a change in the enzyme concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changing factors of the activity of angiotensin converting enzyme of renal brush border in rats]. 165 46

1. Biochemical changes in male, Wistar rats, treated with different doses of 1,2-dichloropropane (50-500 mg kg-1 body weight), were investigated at the end of a 4-week treatment and after a 4-week recovery period. 2. The behaviour of Phase I and Phase II metabolic steps and of the angiotensin converting enzyme activity of the renal proximal tubule brush border were determined. 3. Phase II is more affected by the solvent than Phase I metabolism, and liver metabolism is more affected than the kidney. 4. Angiotensin converting enzyme activity from the proximal tubule brush border appears to be the most sensitive parameter of kidney involvement during treatment. 5. After a 4-week recovery period all the metabolic indices together with angiotensin converting enzyme activity have returned to normal. Only liver reduced glutathione content shows a slight, but significant, increase for the highest dose (500 mg kg-1 body weight). 6. The results show that the biochemical changes induced in liver and kidney by 1,2-dichloropropane are reversible.
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PMID:Recovery of biochemical changes induced by 1,2-dichloro propane in rat liver and kidney. 167 46

There has been considerable interest in the existence of an intrarenal renin-angiotensin system and its physiological implications. Recent demonstrations of renin, angiotensinogen and angiotensin converting enzyme messenger (m)RNAs in the kidney have provided strong evidence for the presence of an independent local system. This has been further supported by the demonstration of tissue-specific regulation of renin and angiotensinogen mRNA expression which may lead to differential systemic and intrarenal angiotensin activities. Using in situ hybridization, we have localized the intrarenal sites of gene expression and possible angiotensin production. One major site appears to be the proximal tubule, where local angiotensin can regulate sodium reabsorption and urine pH. Renin and angiotensinogen mRNA expressions are regulated by several common factors. In particular, sodium depletion stimulates the expression of both genes in the kidney, increasing the production of intrarenal angiotensin that is important in maintaining sodium homeostasis. Renal renin and angiotensinogen mRNA levels are altered in experimental heart failure and the spontaneously hypertensive rat (SHR). These changes in intrarenal renin and angiotensinogen mRNA expression may be important in the renal pathophysiology of these diseases.
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PMID:Molecular biology and pathophysiology of the intrarenal renin-angiotensin system. 255 71

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
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PMID:Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. 262 Jul 97

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. 267 Jun 57

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.
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PMID:Site of entry of kininase II into renal tubular fluid. 283 Nov 47

The distribution of kininases along microdissected nephron segments was studied. Single nephrons from collagenase treated rabbit kidney were microdissected and divided into following 9 segments: glomerulus; early proximal tubule; middle proximal tubule; late proximal tubule; cortical thick ascending limb; distal convoluted tubule; connecting tubule; cortical collecting tubule; medullary collecting tubule. Kininase activities in these nephron segments were measured with or without kininase II inhibitor. Kininase II and other peptidases were mainly localized in glomeruli and whole part of the proximal tubules.
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PMID:Distribution of kininase activity along the rabbit nephron. 303 11

The effects of nonpressor doses of intravenous angiotensin II and of the converting enzyme inhibitor captopril on renal excretory function were investigated in eight healthy volunteers during sustained water diuresis on a constant intake of 150 mmol sodium per day. The angiotensin II-analogue val5-angiotensin II-asp1-beta-amide was infused i.v. at an average dose of 2.6 ng kg-1 min-1 which was the highest dose without a significant effect on arterial blood pressure. This subpressor dose of angiotensin II significantly decreased urine volume, urinary excretion of sodium, chloride and phosphate and distal delivery [(CH2O + CCl)/GFR X 100] in the absence of changes in GFR or distal fractional chloride absorption [CH2O/(CH2O + CCl)]. In a second series of experiments, an oral dose of 50 mg of the angiotensin I-converting enzyme inhibitor captopril was given to the sodium replete volunteers. In this study, captopril did not affect arterial blood pressure, GFR or any of the determined parameters of renal tubular function. Our results strongly suggest that the nonpressor dose of angiotensin II induced renal retention of sodium chloride via increased absorption in the proximal tubule. Thus, they further support the concept that angiotensin II participates in the regulation of renal sodium chloride excretion by affecting proximal tubular absorptive capacity. However, in the sodium replete stage, angiotensin II is of no major importance in regulating sodium chloride excretion.
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PMID:Effect of angiotensin II and captopril on renal tubular function in man. 388 28


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