Angiotensin I Converting Enzyme in Glycerol-Induced Acute Renal Failure in Rats

Angiotensin I converting enzyme (ACE) activity was measured in serum, urine, and tissues of rats with acute renal failure (ARF) induced by glycerol. Glycerol-injected rats were subdivided in three groups according to the urinary volume: oliguric, nonoliguric, and polyuric. The damage to the proximal tubule was evident by (a) the histological analysis at light and electron microscopy level, (b) the augmented urinary excretion of the enzymes dipeptidyl aminopeptidase IV and N-acetyl-β-D-glucosaminidase, and (c) the low molecular weight proteinuria pattern. On the other hand, the appearance of the glomeruli at the ultrastructural level was normal. These data suggest that the increased urinary excretion of enzymes and proteins in these rats is a consequence of the tubular injury. ARF was markedly higher in the oliguric rats. Urine ACE activity increased in the rats of the three groups, but statistical significance was reached only in the oliguric rats. Serum ACE activity increased in the oliguric rats and tissue ACE activity did not change. It is concluded that the high urinary ACE in glycerol-treated rats is associated with the damage to the kidney tubules. These data support the contention that urinary ACE may be another marker of injury to the proximal tubule.     

Angiotensin I Converting Enzyme Activity in Uranyl Nitrate Induced Acute Renal Failure in Rats

Although complete blood count is routinely ordered in most upper urinary tract infections (UTI), and information regarding the patient's platelet indices is made available without added cost, the relationship between platelet count and mean platelet volume (MPV) and specific platelet responses to different infectious agents has not been extensively characterized in UTI. The objectives of this study were to examine platelet counts and platelet indices in children with culture-proven upper UTI to determine if there are organism-specific platelet responses. A retrospective analysis of data from all pediatric urine samples processed at Fatih University Medical School microbiology laboratory was undertaken for a period of two years (January 1, 2005, to December 31, 2006). Of the 200 patients with positive urine cultures, 146 (73%) were infected with gram-negative bacteria and 54 (27%) grew gram-positive bacteria. The platelet count during the episode of upper UTI and the incidence of thrombocytosis was significantly higher with the gram-positive infections than with the gram-negative infections or controls (p < 0.05). A statistically significant higher MPV was detected in the subjects with upper UTI (p < 0.05). Also, our data showed a statistically significant increase in MPV with gram-positive infections compared with the other groups (p < 0.05). In conclusion, based on the importance of the hemostatic component in the pathophysiology of infections, our findings of platelet count and MPV and predictivity of the type of the organism would suggest the usefulness of the routine measurements in children with upper UTI.     

Angiotensin Converting Enzyme in the Testis and Epididymis of Mammals

Summary: Angiotensin converting enzyme (ACE) activity has been reported in testis and epididymis of seven different animal species. Among all the species, the mouse testis and epididymis showed the highest converting enzyme activity followed by rat testis and epididymis. The lowest activity was detected in buffalo testis and rabbit epididymis. Most of the testicular enzyme was found concentrated in the 107,00 xg sediment while the epididymal enzyme was equally distributed between sediment and supernatant. ACE levels of different regions of the rat testis and epididymis was analyzed. The gradient of ACE was found increasing from caput to cauda. A major fraction of testicular and epididymal ACE activity was found in their respective fluid. ACE appeared only in mature rats, rabbits and mice testis and epididymis. Sexually stimulated rabbits showed significant ACE increase in the testis. In vitro characterization studies were conducted. Zusammenfassung: Angiotensin-Converting-Enzym in den Hoden und Nebenhoden von Säugetieren Es wird berichtet über die Aktivität des Angiotensin-Converting-Enzyms (ACE) in den Hoden und Nebenhoden sieben verschiedener Tierarten. Von alien Arten zeigten die Hoden und Nebenhoden der Maus die höchste Enzymaktivität, gefolgt von den Hoden und Nebenhoden der Ratte. Die niedrigste Aktivität wurde in Büffelhoden und Kaninchennebenhoden gefunden. Der größte Teil des Hodenenzyms was in dem UI-trazentrifugensediment (107.000 × g) konzentriert, wohingegen das Nebenhodenenzym gleichmäßig auf das Sediment und den Überstand verteilt waren. Es wurden die ACE-Konzentrationen verschiedener Anteile des Rattenhodens und -nebenhodens bestimmt. Die ACE-Konzentration nahm dabei vom Kopf zum Schwanz hin zu. Der Hauptanteil der Hoden- und Nebenhoden-ACE-Aktivität wurde in den jeweiligen Flüssigkeitsanteilen gefunden. Das ACE tritt nur in geschlechtsreifen Ratten-, Kaninchen- und Mäusehoden und -nebenhoden auf. Sexuell stimulierte Kaninchen wiesen einen signifikanten ACE-Anstieg in den Hoden auf. Die Untersuchungen zur in-vitro-Bestimmung wurden aufgezeigt.     

Androgen Dependence of Testicular and Epididymal Angiotensin Converting Enzyme

Treatment with cadmium chloride (CdCl2) and cyproterone acetate (CA) depressed angiotensin converting enzyme (ACE) activity significantly in testes and epididymal regions of the adult rats compared to the corresponding untreated controls. Exogenous testosterone to CA-treated rats significantly increased the enzyme activity both in the testes and epididymis, the effect in the latter being very significant comparable to CA-treated and untreated controls. Testosterone failed to induce ACE activity in the testes and caput epididymis of 30 day-old immature rats, but the enzyme activity was detected in corpus and cauda epididymis. Our findings indicate that ACE activity in the testicular complex is possibly linked with androgen and is concerned with spermatogenesis and sperm maturation.     

Angiotensin Converting Enzyme in Semen and its Possible Role in Capacitation

Angiotensin Converting Enzyme (ACE) is present in the testis, epididymis and semen. But no physiological role has been assigned to ACE. The present study is to indicate possible role of ACE in capacitation. Semen was incubated in minimum capacitation in vitro. Epinephrine and serotonin were added to note the effect of biogenic amines. The leakage of ACE was very high in capacitated spermatozoa compared to spermatozoa in saline. Presence of amines in the saline induced ACE leakage. These results indicate that ACE may be involved in the capacitation.     

Letter to the Editor: Angiotensin Converting Enzyme Inhibitors and Contrast-Induced Nephropathy

The available data on the use of angiotensin-converting enzyme inhibitors, and the associated risks for contrast-induced nephropathy are sparse and conflicting. Nevertheless, it is a common practice to hold angiotensin-converting enzyme inhibitors before contrast media administration. The reduction of renal blood flow that occurs following the administration of contrast media may be due to the renin-angiotensin–aldosterone system causing constriction of the afferent arterioles. The influence of angiotensin–converting enzyme inhibitor administration on the development of contrast-induced nephropathy was discussed in this letter.     

Angiotensin Converting Enzyme Inhibitor Therapy in Severe Postcardiotomy Dysfunction: A Prospective Randomized Study

Abstract Background: Occurrence of severe postcardiotomy dysfunction requiring prolonged postoperative support with intra-aortic balloon counterpulsation (IABP) and inotropes, complicating surgery for coronary artery disease and valvular heart disease carries important hospital morbidity and mortality. This study evaluated the impact of angiotensin converting enzyme inhibitor (captopril) therapy in these patients in the early postoperative period. Methods: During a 5-year period, 298 patients with prolonged diminished cardiac output required support (> 48 to 72 hours) with IABP plus two or three inotropes. This cohort was randomized to two groups, group A (195 patients) who were continued on IABP and inotropes alone and group B (103 patients) who were given an angiotensin converting enzyme (ACE) inhibitor, captopril 48 to 72 hours postoperatively and continued on IABP and inotropes. Results: Tissue perfusion and he-modynamic parameters improved (p < 0.0001) in group B with early termination of IABP (duration of support mean 86 hours in group B vs 169 hours in group A) and inotropes. Peak improvement in tissue perfusion and hemodynamic parameters correlated with decreased serum angiotensin converting enzyme levels. Hospital mortality occurred in 31% of patients in group A and 14.5% in group B. Morbidity complications developed in 37% of patients in group A and 20% in group B. The average length of hospital stay in group A was 27 days and 17 days in group B. Cardiac, pulmonary, infective, gastrointestinal, renal, and neurological complications were common in both groups. Conclusion: Administration of ACE inhibitors in the early postoperative period to patients with severe postcardiotomy dysfunction caused improvement in tissue perfusion with decreases in mortality, morbidity, and length of hospital stay. These drugs, by effectively limiting physiological effects induced by renin angiotensin-aldosterone axis and other mechanisms, caused recovery of stunned myocardium. More randomized trials are needed before recommending these drugs for routine use in similar patients. (J Card Surg 1998;13;11–17)     

Age Related Development of Angiotensin Converting Enzyme in Testes and Epididymis of Rat

Altersabhängige Entwicklung von Angiotensin-Converting-Enzym (ACE) in den Hoden und Nebenhoden der Ratte
ACE wurde in den Hoden und in verschiedenen Bereichen des Nebenhodens der Ratte unterschiedlichen Alters untersucht. Die ACE-Aktivität erreichte ihren Gipfel, wenn die Tubuli seminiferi die Spermatozoenproduktion des Erwachsenenstadiums aufwiesen; sie pendelte sich auf dieser Höhe danach ein. Die Spitzenkonzentration im Nebenhoden wurde später beobachtet als im Hoden. Der Konzentrationsgrad im Nebenhoden war proportional zum Grad der Spermatozoenreifung und zur Fertilität; die höchste ACE-Aktivität im Nebenhoden fand sich im Kopfbereich.     

二尖瓣病变患者血浆血管紧张素转换酶水平与心房颤动的关系

目的探讨二尖瓣病变患者血管紧张素转换酶（angiotensin converting enzyme,ACE）水平与持续性心房颤动（atrial fibrillation,Af）的关系。方法124例拟行心瓣膜置换术的二尖瓣病变患者纳人本研究,所有患者术前均进行血生化、心电图、彩色超声心动图及胸部X线片检查。根据是否伴有持续性Af将124例患者分为窦性心律（sinus rhythm,SR）组（SR组）和Af组;在Af组,根据患者的二尖瓣病变类型,进一步分为二尖瓣狭窄（mitral stenosis,MS）伴Af组（MS—Af组）和二尖瓣反流（mitral regurgitation,MR）伴Af组（MR—Af组）。采用竞争放射免疫法测定各组的ACE水平。结果二尖瓣病变患者中47．58％（59／124）伴有Af,与二尖瓣反流相比,二尖瓣狭窄较多伴有持续性Af（60．53％vs．27．08％,P〈0．05）。Af组的血浆ACE水平明显高于SR组（72．60±22．03U／L vs．56．40±17．96U／L,P〈0．05）。在Af患者中,MS—Af组的ACE水平高于MR—Af组（82．92±18．75U／L vs．66．25±21.10U／L,P〈0．05）,且易伴有血栓。多元回归分析显示：Af与ACE水平（r=0．089,P=0．021）及左房直径（r=0．447,P=0．033）有关。结论二尖瓣病变患者血浆ACE水平升高与Af发生有关,在二尖瓣狭窄伴Af的患者中ACE水平升高更为明显;ACE水平与左心房血栓形成有一定的关系。     

Elevated Urinary Albumin Excretion is not Linked to the Angiotensin I-converting Enzyme Gene Polymorphism in Clinically Healthy Subjects

An elevated urinary albumin excretion (UAE) in non-diabetic subjects without renal or cardiovascular disease has been shown to be predictive of ischaemic heart disease. An insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene has been identified and the D allele may be associated with cardiovascular disease. The aim of this study was to find a potential linkage between this polymorphism and elevated UAE. For studies of UAE and cardiovascular pathophysiology, a highly selected population sample has been identified comprising all clinically healthy subjects aged 40-65 years with elevated UAE in a dipstick negative urinary sample (n = 27) from The Copenhagen City Heart Study. Neither the ACE genotype distribution (p = 0.12) nor the D and I allele frequencies (p = 0.69) differed significantly between subjects with elevated UAE and a matched normoalbuminuric control group (n = 46). Elevated UAE in clinically healthy subjects is not linked to the ACE gene polymorphism.     

Changes in Angiotensin Converting Enzyme in Testes and Epididymes of Rat Due to Serotonin Administration

Effect of exogenous serotonin and blockade of its endogenous production on Angiotensin Converting Enzyme (ACE) in testes and epididymis was studied. Serotonin (30 mg/kg) and p-chlorophenylalanine (100 mg/kg) were injected for 4 and 3 days respectively. Serotonin reduced the weights of testes, seminal vesicle and ventral prostate whereas epididymal weight increased due to fluid accumulation. ACE was significantly reduced in tissue and fluid fractions of testes and epididymis of serotonin treated rats. pCPA had no effect on ACE levels. Serotonin seems to have direct effect on epididymis also.     

血管紧张素转化酶2-血管紧张素(1-7)-Mas轴与肾脏

血管紧张素转化酶2-血管紧张素(1-7)-Mas轴是肾素-血管紧张素系统的一个新分支,该轴能对抗血管紧张素Ⅱ(AngⅡ)、调节心血管和肾脏功能,发挥降低血压、保护心血管功能,Ang(1-7)在调节肾脏血管、小管转运、细胞生长、血压方面均发挥重要作用.本文就该轴的生物学特点及其对肾脏的影响作一综述.     

Risk of Osteoporotic Fractures With Angiotensin II Receptor Blockers Versus Angiotensin‐Converting Enzyme Inhibitors in Hypertensive Community‐Dwelling Elderly

Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used to treat hypertension; however, in vivo and clinical studies suggest that ARBs and ACE inhibitors may exert different effects on bone. The association between long‐term use of ARBs and ACE inhibitors and fracture requiring medical attention is limited. We conducted a population‐based, retrospective cohort study with propensity score matching using administrative databases in Ontario, Canada, to examine the risk of osteoporosis‐related fractures in hypertensive elderly treated with ARBs versus ACE inhibitors. We identified a cohort of newly treated hypertensive patients aged 66 years and older who initiated an ACE inhibitor from May 1, 2004, to March 31, 2012, and matched them to ARB users on propensity score, sex, and age at drug initiation. The primary outcome was hip fracture, and secondary outcomes were non‐hip major osteoporotic fractures (other femoral, clinical vertebral, forearm, wrist, humerus) and other osteoporotic fractures (pelvis, clavicle, patella, shoulder, upper arm, tibia, fibula, ankle, scapula, ribs, sternum, trunk). We calculated hazard ratios (HRs) using Cox proportional hazards model with robust standard errors. Of the 87,635 patients who initiated treatment, 28,819 (32.9%) started ARBs and 58,816 (67.1%) started ACE inhibitors. Among new ARB users, 27,815 (96.5%) were successfully matched to ACE inhibitor users. Without dose adjustment, no significant association was observed for ARBs relative to ACE inhibitor users for hip fractures (HR = 0.88; 95% confidence interval [CI] 0.70–1.11), with a decreased risk of other major osteoporotic fractures (HR = 0.81; CI 0.70–0.93) and no significant association for other osteoporotic fractures (HR = 0.88; CI 0.74–1.05). When adjusted for dosage, there was no significant difference between the effects of ARBs and ACE inhibitors on hip (HR = 0.99; CI 0.78–1.25), other major osteoporotic (HR = 0.87; CI 0.75–1.01), and other osteoporotic fractures (HR = 0.90; CI 0.74–1.08). © 2014 American Society for Bone and Mineral Research.     

Contrasting Effects of Acute Angiotensin Converting Enzyme Inhibitors and Calcium Antagonists in Transplant Renal Artery Stenosis

Deterioration of renal function is a major concern during treatmentby converting enzyme inhibitors of hypertensive kidney recipientswith transplant renal artery stenosis. However, there has beenno assessment of the frequency of this complication and itsspecificity for converting enzyme inhibitors as compared toother antihypertensive drugs. The effect of acute administrationof captopril on mean arterial pressure, glomerular filtrationrate (GFR) (creatinine clearance) and effective renal plasmaflow (clearance of ¹³¹I-hippuran) was assessed in eight hypertensivepatients with transplant renal artery stenosis. Captopril induceda decrease in mean arterial pressure (128±6–121±7mmHg) and a reduction in GFR (59±8–44±8ml/minper 1.73m², P<0.05). The decrease in GFR was observed inseven out of eight patients and varied between 0% and 100% ofthe pre-captopril value. Effective renal plasma flow was maintained(157±47–141 ±24m1/min per 1.73m²) and filtrationfraction decreased by 15±7%. The effect of captoprilwas compared to that of nifedipine (N=20 mg) in four patients.Despite a larger decrease in mean arterial pressure (130±7–109±10mmHg), no reduction in GFR was observed (68±13–71.4±8).Effective renal plasma flow was unchanged and filtration functionslightly increased. Surgical or percutaneous transluminal angioplastyin five patients suppressed the captopril-induced decrease inGFR. We conclude that (1) renal insufficiency induced by convertingenzyme inhibitors is frequent in severe transplant artery stenosis;(2) renal function is well maintained during nifedipine-inducedreduction in blood pressure; (3) renal insufficiency inducedby converting enzyme inhibitors is not due to reduction of systemicblood pressure but to intrarenal effects of angiotensin II.     

Acute Renal Failure Induced by Angiotensin Converting Enzyme Inhibitor in a Patient with Polyarteritis Nodosa

We report a patient who presented with malignant hypertension and renal failure. He was treated with lisinopril, spironolactone, and nifedipine retard for blood pressure control. Subsequent renal function showed further deterioration, but it then improved after withdrawal of the angiotensin converting enzyme inhibitor (ACE I). The diagnosis of classical polyarteritis nodosa was established with aneurysmal dilatation demonstrable in the renal vasculature. His renal impairment improved further following immunosuppressive therapy and the disease has remained inactive 4 years after first presentation. This is the first reported case of acute renal failure associated with the use of ACE I in polyarteritis nodosa.     

Involvement of Renin-Angiotensin System in Pressure-Flow Relationship: Role of Angiotensin-converting Enzyme Gene Polymorphism

Background: The renin-angiotensin system is involved in blood pressure regulation. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is known to be associated with variation of plasma and cellular ACE concentrations. Furthermore, changes in arterial function have been suggested to be associated to the DD genotype. The aim of the study was to investigate the arterial vascular response to a physiologic stimulus (i.e., flow) according to the I/D ACE gene polymorphism.

Methods: Sixty patients scheduled for coronary artery bypass grafting (n = 24) or valve surgery (n = 36) under normothermic cardiopulmonary bypass were genotyped in a blind manner by polymerase chain reaction. Mean arterial pressure was measured at pump flows ranging from 1 to 3 l [middle dot] min-1 [middle dot] m-2 by 0.25 l [middle dot] min-1 [middle dot] m-2 step each 15 s, to obtain a pressure-flow relation. Independent factors associated with the variation of the slope of the pressure-flow relation curve were assessed by multivariate analysis.

Results: We found a D allelic frequency of 0.54. Patients were separated in two groups (DD, n = 16;ID/II, n = 44). There were no significant difference with regard to preoperative and intraoperative data between the two groups. DD patients had their pressure-flow relation curves shifted upward (with higher pressures as flow increased), indicating a lesser decrease in vascular resistance. Furthermore, DD genotype was the only independent predictor of the slope of the curves (21.5 +/- 4.2 vs. 18.1 +/- 5 mmHg/[l [middle dot] min-1 [middle dot] m-2] for DD and ID/II, respectively;P = 0.02; values are mean +/-SD).     

Study of Serum and Tissues Angiotensin Converting Enzyme (ACE) Activity in Rat with Gentamicin Induced Renal Toxicity

Purpose.?In this research ACE activity (as a marker of epithelial injury) was studied in rats with gentamicin induced renal toxicity. Methods.?Male Sprague-Dawley rats were sacrificed 1, 3, 5, and 7 days after gentamicin injection, 100 mg/kg/day for 1, 3, 5, and 7 consecutive days. ACE activity was measured in serum, kidney and lung. These data were compared with normal saline-treated rats. Histological scoring of renal cortical pathology was performed on days 1, 3, 5, and 7. Results.?Treatment of rats with gentamicin resulted in renal damage evidenced by proteinuria, polyuria, and decreased creatinine clearance. The damage to the kidney proximal tubule was evident by (a) the histological analysis at light microscopy and (b) the augmentation in the urinary excretion of N-acetyl-β-d-glucosaminidase (NAG). Kidney ACE activity decreased while lung and serum ACE activity didn’t change until day 7. Lung ACE activity increased significantly on day 7. Kidney and serum ACE activity increased too. Blood pressure increased significantly on day 7. This corresponded well with the lung ACE activity increment. Conclusion.?These data suggest that kidney ACE activity decreased significantly just one day after gentamicin administration and prior to kidney NAG decrease.     

The Effects of Angiotensin Converting Enzyme Inhibitors on Potassium Homeostasis in Dialysis Patients With and Without Residual Renal Function

Hyperkalemia is exacerbated by angiotensin converting enzyme inhibitors (ACE‐I). Distal potassium (K⁺) secretion is negligible in anuric patients. ACE‐I therapy may reduce renal, peritoneal, and colonic K⁺ losses. We examined the effect of ACE‐I therapy on serum, urinary, and dialysate K⁺ in a cross‐section of peritoneal and hemodialysis patients. Serum, 24‐h urine K⁺, and peritoneal dialysate excretion K⁺ levels were measured and the results were compared in the various dialysis and treatment groups. Eighty‐one hemodialysis (HD) and 32 peritoneal dialysis (PD) patients were included. Serum K⁺ in HD patients with no residual renal function (RRF) was higher in those receiving ACE‐I therapy (P = 0.02). Serum K⁺ levels in HD patients receiving ACE‐I treatments with RRF was similar to that in oligoanuric HD patients not receiving an ACE‐I. Urinary K⁺ excretion was significantly reduced in those on ACE‐I therapy versus those not on an ACE‐I (P < 0.05). Mean serum K⁺ was lower in PD versus HD patients (P < 0.05). PD patients with no RRF on ACE‐I therapy had higher serum K⁺ concentrations (P = 0.002) and dialysate K⁺ excretion was lower (P = 0.05), in comparison with PD patients not on an ACE‐I. PD patients with RRF on ACE‐I therapy had higher serum K⁺ concentrations compared with those not on ACE‐I therapy (P = 0.03). Both urinary and dialysate K⁺ excretion were reduced (P = 0.001 and P = 0.002, respectively). ACE‐I therapy increases serum K⁺ concentration in dialysis patients. PD patients have relatively lower serum K⁺ levels compared with HD patients. In PD patients, ACE‐I therapy reduces dialysate K⁺. These changes may result from reduced peritoneal movement of K⁺.     

Calcitonin Receptor Gene Polymorphism in Japanese Women: Correlation with Body Mass and Bone Mineral Density

We have identified a polymorphism at position 1377 of the calcitonin receptor (CTR) gene which generates CC, CT, or TT genotype. In this study, the genotypes of the CTR and their relationship with the body height, the body weight, the bone mineral density (BMD), and osteocalcin levels were examined in 152 healthy Japanese women aged 16-43 years. The CTR genotypic frequencies in the Japanese population were 77.0% for CC, 20.4% for CT, and 2.6% for TT. The height, BMD, and osteocalcin levels were not significantly different among these three genotypes. The body weight adjusted for height in these three groups was significantly different in the order of TT, CT, and CC (P = 0.0454 by analysis of covariance). In combined analysis of the VDR genotype (B,b) and the CTR genotype (C,T), the body height was found to be significantly different between CCB and others (P = 0.0236). In addition, analysis of the CTR genotypic frequency using 64 blood samples from Japanese and 47 blood samples from Caucasians indicated that there was a significant difference between the two races (P < 0.0001). We found that C allele was predominant in the Japanese population, however, Caucasians have an almost equal ratio of the C and T. In conclusion, the CTR allele is one of the genetic factors regulating body weight in Japanese women.