Abstract:
BACKGROUND:The direct renin inhibitor aliskiren is known to exhibit a strong antihypertensive effect. However, the organoprotective potential of aliskiren beyond its antihypertensive properties is less clear. This study investigates the antifibrotic nephroprotective effects of aliskiren in a nonhypertensive mouse model for progressive renal fibrosis. METHODS:COL4A3(-/-) mice received aliskiren via osmotic minipumps. Placebo-treated animals served as controls. Therapy was initiated in 6-week-old animals already showing renal damage (proteinuria ~1 g/l, starting renal fibrosis) and lasted for 4 weeks. Six animals were sacrificed after 9.5 weeks; serum urea and proteinuria were measured. Kidneys were further investigated using histological, immunohistological, and western blot techniques. Survival until end-stage renal failure was monitored in the remaining animals. RESULTS:COL4A3(-/-) mice did not develop hypertension. Aliskiren serum levels were in the therapeutic range (288 ± 44 ng/ml). Therapy significantly prolonged lifespan until death from renal failure by 18% compared with placebo-treated controls (78.6 ± 8.2 vs. 66.6 ± 4.9 days, P < 0.05). Similarly, therapy reduced the amount of proteinuria and serum urea. Compared with placebo-treated controls, the accumulation of extracellular matrix and renal scarring and the levels of transforming growth factor-β (TGFβ) and connective tissue growth factor (CTGF) were decreased in treated mice. CONCLUSIONS:Despite the late onset of therapy, our results indicate nephroprotective effects of the renin inhibitor aliskiren beyond its antihypertensive property in this animal model of progressive renal fibrosis. In addition to the recognized antihypertensive action of aliskiren, its antifibrotic, antiproteinuric effects demonstrated in the present study indicate that aliskiren may have potential as an important therapeutic option for chronic fibrotic diseases in humans.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Gross O,Girgert R,Rubel D,Temme J,Theissen S,Müller GAdoi
10.1038/ajh.2010.231subject
Has Abstractpub_date
2011-03-01 00:00:00pages
355-61issue
3eissn
0895-7061issn
1941-7225pii
ajh2010231journal_volume
24pub_type
杂志文章abstract::The purpose of this study was to investigate whether acute hyperinsulinemia induces selective hemodynamic effects in the mesenteric, renal, and iliac vascular beds, and to determine whether nitric oxide (NO) plays a role in the regulation of blood flow and mean arterial pressure (MAP) during acute hyperinsulinism. In ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(98)00133-2
更新日期:1998-10-01 00:00:00
abstract::To evaluate the possible physiologic role of atrial natriuretic factor (ANF) in the observed dissociation of aldosterone secretion from the renin-angiotensin system during hypoxic exercise, 12 untrained men, ages 18 to 24, were studied on two separate days for 30 min during hypoxic (16% O2) and normoxic (room air) exe...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/4.4.341
更新日期:1991-04-01 00:00:00
abstract::Although the most direct way to interfere with the renin-angiotensin system (RAS) is at the level of the angiotensin II (AII) receptor, the currently available AII receptor antagonists are peptides still retaining significant agonistic properties with the obvious drawbacks of limited stability and lack of oral activit...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/3.8.599
更新日期:1990-08-01 00:00:00
abstract::Salt-sensitive persons have lower plasma renin activity than salt-resistant persons and their plasma renin activity increases less with a low sodium diet or volume depletion, compared to salt-resistant individuals. However, the time course of the renin response to acute volume contraction has not been studied in human...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1016/s0895-7061(01)02226-9
更新日期:2002-01-01 00:00:00
abstract::Barriers to high blood pressure (HBP) care and control have been reported in the literature for > 30 years. Few reports on barriers, however, have focused on the young black man with HBP, the age/sex/race group with the highest rates of early severe and complicated HBP and the lowest rates of awareness, treatment, and...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0895-7061(99)00121-1
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:As hypertension, obesity, and leanness are reported to be associated with poor cognitive function, it is possible that obesity or leanness in hypertensive patients may also be associated strongly with poor cognitive function. METHODS:We recruited 184 elderly hypertensive patients comprising 93 very elderly ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2008.157
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:Endothelial progenitor cells (EPCs) provide paracrine support to the vascular endothelium and may also replace damaged or senescent endothelial cells. Low numbers of endothelial progenitor colony-forming units (CFU-ECs) in culture are a predictive biomarker of vascular disease. We hypothesized that the numbe...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.101
更新日期:2009-09-01 00:00:00
abstract::Increased dietary K+ increases plasma [K+] and is linked to or associated with reduced mortality from stroke and reduced blood pressure in humans and animals. We hypothesized that physiologic increases in extracellular [K+] ([K]o) directly inhibit cultured vascular smooth muscle cell (VSMC) proliferation. Studies were...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/7.4.346
更新日期:1994-04-01 00:00:00
abstract::Arterial hypertension is the most common chronic medical condition requiring office visits to physicians and is a major contributing factor to the development of myocardial infarction and stroke. Its importance as a cardiovascular risk factor is at least as significant in women as in men; however, the ever-growing lit...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(97)00330-0
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND:Both increased night blood pressure (BP) and nondipping are associated with worse cardiovascular risk and prognosis. However, as they are often related features, their relative importance has been difficult to assess separately. In this study we address separate associations of nocturnal hypertension and non...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpt175
更新日期:2014-05-01 00:00:00
abstract::Several epidemiological and clinical studies have established a clear association between alcohol consumption and hypertension. The mechanism of the pressor effect of ethanol is not well understood. We studied the in vitro effects of increasing amounts of ethanol on different Na+ transport systems from human erythrocy...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/2.10.784
更新日期:1989-10-01 00:00:00
abstract::Arterial stiffness has been known as a sign of cardiovascular risk since the 19th century. Despite this, accurate measurement and clinical utility have only emerged in recent times. Arterial stiffness and its hemodynamic consequences are now established as predictors of adverse cardiovascular outcome. They are easily ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1038/ajh.2010.192
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Type B acute aortic dissection (AAD) carries a high short- and midterm mortality rate; however, knowledge related to long-term outcome is largely incomplete. The objective of this study was to identify long-term predictors including antihypertensive medications in type B AAD. METHODS:We conducted a clinical...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.5
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND:Recent reports suggesting that primary aldosteronism (PA) is more common than historically thought have often relied on use of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to identify patients with PA. Prior determinations of the validity of the ARR had been generally...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.01.002
更新日期:2005-06-01 00:00:00
abstract::Angiotensin II (Ang II) plays important roles in the development of cardiovascular diseases including hypertension, renal diseases, cardiac hypertrophy, congestive heart failure, and ischemic heart disease. Angiotensin II exerts classic hemodynamic and renal effects, but it is also a local biologically active mediator...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/j.amjhyper.2005.05.005
更新日期:2005-09-01 00:00:00
abstract::The changes induced by transient hypertension on cardiac structure and function are unclear. Pregnancy-induced hypertension offers a natural and spontaneous model of this condition. To assess the potential of echocardiographic Doppler to unmask left ventricular function impairment, we studied 28 women aged 26.4 +/- 7....
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(00)01264-4
更新日期:2001-03-01 00:00:00
abstract::Although left ventricular hypertrophy (LVH) is an adaptive response to the increased load imposed on the heart in patients with hypertension, it ultimately is itself a major risk factor for cardiovascular disease. The influence of LVH on left ventricular function and on the coronary circulation, and the occurrence of ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/6.3.14s
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND:The renin-angiotensin system (RAS) plays a major role in promoting left ventricular (LV) remodeling in essential hypertension. We designed a controlled, randomized pilot study aimed to test the hypothesis that the dual RAS blockade with angiotensin-converting enzyme (ACE) inhibitor (ACEi) + angiotensin II re...
journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1038/ajh.2007.47
更新日期:2008-02-01 00:00:00
abstract::The Captopril Prevention Project (CAPPP) is an ongoing prospective intervention study in 10,800 hypertensive patients in Sweden and Finland. Patients are randomized to treatment with either conventional antihypertensive therapy, ie, diuretics or beta-blockers, or the angiotensin-converting enzyme inhibitor captopril. ...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-09-01 00:00:00
abstract::The insulin sensitivity of five essential hypertensive patients was compared to five patients with renovascular hypertension, five patients with primary hyperaldosteronism, and five normotensive subjects, using the euglycemic hyperinsulinemic clamp technique. Essential hypertensive patients had significantly lower ins...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/5.1.26
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Recent studies have revealed the existence of bone marrow-derived endothelial progenitor cells (EPCs). The number of circulating EPCs might reflect the pathogenesis of atherosclerosis and progression of cardiovascular diseases (CVDs). The purpose of this study was to evaluate the relationship between the num...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2008.278
更新日期:2008-11-01 00:00:00
abstract::A negative calcium balance has previously been described in human hypertension with low levels of plasma ionized calcium (Ca2+) and an increased urinary excretion of calcium. The cause of this disturbance in mineral metabolism is not known, nor is it known if this derangement could be abolished if blood pressure is re...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/7.4.302
更新日期:1994-04-01 00:00:00
abstract:BACKGROUND:Sustained hypotension after an acute dynamic exercise bout is due primarily to peripheral vasodilation. We tested the hypothesis that adenosine-mediated vasodilation contributes to hypotension after exercise, by determining the effect of blocking its actions with caffeine. METHODS:Fourteen healthy middle-ag...
journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.amjhyper.2005.07.022
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:In the hypertensive heart, epicardial arteries are not enlarged, despite increased total coronary flow related to augmented cardiac workload, wall stress, and left ventricular (LV) mass. The aims of this study were to assess the impact of different hemodynamic factors and LV mass on baseline left main corona...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.07.003
更新日期:2007-03-01 00:00:00
abstract::Despite intense investigation and clinical attention, many challenges remain in the management of the hypertensive patient. It is clear that hypertension remains inadequately controlled worldwide, with the control rate in the United States approximating 27%. Furthermore, several recent studies have underscored that it...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(02)02948-5
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:High salt diet causes cardiac hypertrophy and fibrosis and increases cardiac aldosterone, while decreasing plasma aldosterone. The present study assessed, in Wistar rats, the effect of high salt diet on left and right ventricle (LV and RV, respectively) weight and fibrosis both with and without the aldostero...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(02)03268-5
更新日期:2003-04-01 00:00:00
abstract::Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(02)02264-1
更新日期:2002-05-01 00:00:00
abstract:BACKGROUND:This study was designed to evaluate whether plasma asymmetric dimethylarginine (ADMA) has any role in predicting hemodynamic responses in clinically healthy young subjects. ADMA, as an endogenous nitric oxide (NO) synthase inhibitor, has been demonstrated to associate with hypertension and vascular reactivit...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2008.215
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Masked hypertension (MHT), defined as normal blood pressure (BP) at office associated with high BP at home, has been shown to be associated with an increased risk of vascular events. However, MHT is poorly known in the elderly, although this age segment is at high risk of hypertension-related vascular events...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.23
更新日期:2011-06-01 00:00:00
abstract::This article examines the results of the Joint National Committee's Fifth Report on the treatment of hypertension (JNC-V), especially regarding the economic arguments put forth therein. Economics are a poor basis for treatment decisions, as the cheapest therapies may not be the best for any given patient. Broad treatm...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/0895-7061(94)P1709-9
更新日期:1994-10-01 00:00:00