Abstract:
OBJECTIVE:Recently, an apparently novel, specific endothelin-1 inactivating metalloendopeptidase (ET-1 peptidase) has been isolated from the rat kidney. In this study we attempted to determine whether the same or a similar peptidase is present in the human kidney, and whether the enzyme is excreted into the urine. The urinary ET-1 peptidase could serve as an indirect index of the renal endothelin system, both in physiology and pathophysiology. METHODS:Kidney specimens were obtained from part of nephrectomized kidneys unaffected by any neoplastic process from six adult patients. The enzyme was purified using differential centrifugation, detergent solubilization of the membrane proteins, ultrafiltration and nondenaturing gel electrophoresis. The enzyme activity assays were performed at pH 5.5 and 37 degrees C in the presence of increasing concentrations of unlabelled peptides and inhibitors using a fixed amount of [125I]ET-1 as substrate. The degradation extent was quantified with trichloroacetic acid precipitation and high performance liquid chromatography. The degrading activity of ET-1 was determined in urine samples from adult patients with hypertension, children with chronic renal failure and those with stable renal allograft RESULTS:ET-1 peptidase from the human kidney displays characteristics close to that of the rat ET-1 peptidase we have recently described (J. Hypertens 1994; 12:1155-1162). The enzyme, a membrane-bound metalloendopeptidase, exhibits low electro- phoretical mobility on nondenaturing gel (Rf 0.08); it is an apparently heterologous structure comprising three enzymatically inactive subunits, it has a pH optimum at 5.5, a nanomolar range affinity to the ET-1 (KM 180 nmol/l) that is hydrolysed to two main degradation products, and a 10-100-fold lower affinity to big ET-1 (KM 11.5 micromol/l), endothelin 11 21 fragment (KM 15.3 micromol/l), endothelin antagonist Trp-Leu-Asp-Ile-Ile-Trp (KM 3.1 micromol/I), gastrin (KM 2.2 micromol/l) and cholecystokinin (KM 4.0 micromol/l). Substance P, neuropeptide Y, atrial natriuretic peptide, bradykinin, angiotensin II and enkephalin were poor substrates for the enzyme. The most powerful inhibitors of the ET-1 peptidase included thiorphan (IC50 0.28 nmol/l), phosphoramidon (IC50 0.55 nmol/l), phenanthroline (IC50 11.5 micromol/l), cyclosporin (IC50 400 micromol/l), phosphate (IC50 1.2 mmol/l), citrate (IC50 0.6 mmol/l) and aniline naphthalene sulphonic acid (IC50 0.25 mmol/l). Our data suggest that three ET-1 degrading peptidases with optimal activity at pH 4.5, 5.5 and 7.0, respectively, are excreted into the urine. The enzyme with a pH optimum 4.5 is of lysosomal origin whereas the two other enzymes correspond by their pH optima to the renal ET-1 peptidase and neutral endopeptidase. We have found statistically significant increases (P < 0.001) in the activity of both lysosomal and ET-1 peptidase in the urine in patients with hypertension and in children with chronic renal failure compared with healthy subjects or children with stable renal allograft CONCLUSIONS:Human kidney contains an acidic, highly specific endothelin-1 inactivating metalloendopeptidase that may have a key role in the regulation of concentrations of renal and circulating endothelins. The enzyme is excreted into the urine where its activity seems to be increased in patients with hypertension and chronic renal failure; it may potentially serve as an indirect index of the renal endothelin system.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Janas J,Sitkiewicz D,Januszewicz A,Szczesniak C,Grenda R,Janas RMdoi
10.1097/00004872-200018040-00018subject
Has Abstractpub_date
2000-04-01 00:00:00pages
475-83issue
4eissn
0263-6352issn
1473-5598journal_volume
18pub_type
杂志文章abstract:OBJECTIVE:To determine whether the decision to treat uncomplicated mild hypertension with drugs, in accordance with the World Health Organization - International Society of Hypertension (WHO/ISH) guidelines based on a series of blood pressure (BP) measurements over 6 months, resulted in the treatment of patients at hig...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917060-00014
更新日期:1999-06-01 00:00:00
abstract:AIM:Since canine hereditary essential hypertension has been previously reported in a colony of Siberian husky dogs, we tested the suitability of this model for use in studies on the platelet defect identified in humans with essential hypertension. METHODS:Platelet aggregation and dense granule ATP secretion were measu...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199210120-00009
更新日期:1992-12-01 00:00:00
abstract:OBJECTIVE:To examine in a population with a high prevalence of hypertension, the association between six cardiovascular polymorphisms, arterial stiffness and medication use. METHODS:In this cross-sectional study (Hypertension: Interaction and Prevalence of POlymorphisms related to Cardiovascular Risk and the Associati...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/hjh.0b013e328317f215
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVES:To provide estimates of the global burden of disease attributable to non-optimal blood pressure by age and sex for adults aged > or = 30 years, by WHO subregion. METHODS:Estimates of attributable burden were made using population impact fractions, which used data on mean systolic blood pressure levels, dise...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000209973.67746.f0
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associat...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200201000-00013
更新日期:2002-01-01 00:00:00
abstract:OBJECTIVE:Work stress contributes to risk of coronary heart disease and hypertension. This study tested the influence of job control on ambulatory blood pressure, and ratings of perceived stress and happiness in men and women systematically sampled by socio-economic status from the Whitehall II epidemiological cohort. ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200405000-00012
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to examine the utility of the generalized transfer function (GTF) and the late systolic shoulder of the radial pressure waveform (SBP2) for estimating seated central systolic blood pressure (c-SBP) and seated c-augmentation index (c-AIx). METHODS:In 199 participants (182 cardiovasc...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32835c1d45
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVES:To assess the consequences of malignant hypertension and its evolution with antihypertensive treatment. BACKGROUND:Malignant hypertension can be considered as a model of the effects of very high blood pressure and renin-angiotensin levels on target organs. However, the consequences on the heart have been li...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283430b12
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVES:Arterial stiffness is associated with excess morbidity and mortality, independently of other cardiovascular risk factors. Age is the main determinant responsible for arterial wall changes leading to arterial stiffening. Environmental and genetic factors may however influence the magnitude of the effects of a...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200103000-00008
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that genetically determined alterations of maternal immune tolerance to a foetal semi-allograft are important for the pathogenesis of hypertensive disorders in pregnancy. DESIGN:A genetic association study was performed to analyse the impact of genetic polymorphisms known to be involve...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000188732.52722.5a
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:Reduction in capillary density or rarefaction is a hallmark of essential hypertension. We measured the retinal capillary density using noninvasive optical coherence tomographic angiography (OCT-A) in adults with treated systemic hypertension and determined possible correlations with ambulatory blood pressure ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001916
更新日期:2019-03-01 00:00:00
abstract:OBJECTIVE:Arterial hypertension is recurrently associated with inflammation of the endothelium as an effect of the upregulation of functional molecules, including cytokines, adhesion molecules and chemokines. However, the role of monocyte chemoattractant protein-1 (MCP-1) in maintaining the inflammatory state of endoth...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000234111.31239.c3
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:To determine whether acutely lowering insulin levels with somatostatin in obese, insulin-resistant hypertensive individuals reduces arterial pressure and forearm vascular resistance; and whether these changes are reversed by restoring insulin levels during continuing somatostatin infusion. SUBJECTS:Subjects ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that sleep-related breathing disorder (SRBD) is associated with increasing severity of cardiovascular risk markers. DESIGN:A cross-sectional study of sleep laboratory patients. SETTING:University Hospital Sleep Disorders Centre. PATIENTS:We studied 591 patients referred for a sleep s...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200104000-00004
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVE:In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction in BP and UAER...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e32834a8a25
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in-utero exposure to antihypertensive treatment is conflicting with many studies suffering from significant methodological issues. METHOD:We c...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002670
更新日期:2020-10-09 00:00:00
abstract:OBJECTIVES:The aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension, and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients. METHODS:...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-199917080-00004
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVES:Studies regarding the effects of parity on blood pressure in later life produced conflicting results. The aim of our study is to analyse whether parity influences the prevalence of hypertension in perimenopausal and postmenopausal women. METHODS:One thousand perimenopausal and postmenopausal women (mean age...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32835c1742
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Coffee is widely consumed in the Western diet and therefore has important implications for public health. Research findings pertaining to the effects of coffee consumption on cardiovascular health are conflicting, and the role of caffeine is not clear. OBJECTIVE:To examine the relationship between coffee in...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/01.hjh.0000249696.19360.be
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:The objective of the study was to investigate interarm differences of blood pressure (BP) and its determinants, and to clarify whether both arms are equally good in assessing BP and target organ damage in the general population. METHODS:We studied a representative sample of Finnish adult population with 484 ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000040
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:To follow the changes in blood pressure and echocardiographically determined left ventricular mass in offspring of mothers who had hypertension during pregnancy. DESIGN:Longitudinal study with a 5-year follow-up. METHODS:Nineteen offspring of mothers who had hypertension during pregnancy, and sustained hype...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract:BACKGROUND:Hypertensive nephrosclerosis is one of the most frequent causes of chronic kidney failure. Proteome analysis potentially improves the pathophysiological understanding and diagnostic precision of this disorder. In the present exploratory study, we investigated experimental nephrosclerosis in the two-kidney, o...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000370
更新日期:2015-01-01 00:00:00
abstract::The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-198808000-00007
更新日期:1988-08-01 00:00:00
abstract:PURPOSE:To study the feasibility of vascular mechanics at the aortic arch with two-dimensional speckle tracking echocardiography, as well as to define normal values and to compare results between hypertensive patients and healthy patients. METHODS:We included 107 patients (61 healthy patients and 46 hypertensive patie...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001336
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVE AND DESIGN:The aim of the study was to assess the role of angiotensin II (Ang II) in the maintenance of cardiovascular hypertrophy and the abnormal vascular amplifier properties in spontaneously hypertensive rats (SHR) with established hypertension. Losartan, a type 1 Ang II receptor antagonist, was administe...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199307000-00006
更新日期:1993-07-01 00:00:00
abstract:OBJECTIVE:To determine the blood pressure responses in elderly normotensive men and women to dietary sodium and to the diunsaturated fatty acid dihomogammalinolenic acid (DGLA), which is derived from linoleic acid. DESIGN:Blood pressure responses were assessed in 66 subjects (36 male, 30 female; mean age 65 years) on ...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-199312000-00011
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism-related differences in ACE concentration do not result in differences in angiotensin levels. METHODS AND RESULTS:To investigate whether this relates to differences in the contribution of the ACE C-domain and N-domain, we quantified, u...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f465d2
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:Blood pressure normally declines during the night ('dipping'); a blunted nocturnal decline is an important cardiovascular risk factor. Marriage may be associated with lower ambulatory blood pressure, although this may be confounded by socio-economic and dietary factors. We examined the association of marital ...
journal_title:Journal of hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/HJH.0000000000000107
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Ambulatory blood pressure (BP) monitoring (ABPM) detects subjects with normal clinic but high ambulatory 24-h BP, that is, masked hypertension. METHODS:One hundred and thirty newly diagnosed obstructive sleep apnea syndrome (OSAS) patients, free of recognized cardiovascular disease were included (111 men, a...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3282f55049
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:Molecular variants of the angiotensinogen (AGT) and the angiotensin II type 1 receptor (ATR) genes have been associated with the risk of coronary artery disease (CAD) and myocardial infarction (MI), but data so far available are conflicting. The primary object of the paper is to verify this possible associati...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200105000-00007
更新日期:2001-05-01 00:00:00