Abstract:
BACKGROUND:In this study, we tested the hypothesis that long-term Rho-kinase inhibition would reverse nitro-L-arginine methyl ester-exacerbated nephrosclerosis in spontaneously hypertensive rats and attempted to elucidate the mechanism involved. METHODS:Five groups (each n = 8) were studied: untreated spontaneously hypertensive rats; nitro-L-arginine methyl ester (50 mg/l in drinking water, for 3 weeks)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester with fasudil (10 mg/kg/day)-treated spontaneously hypertensive rats; nitro-L-arginine methyl ester for 3 weeks followed by fasudil for 3 weeks-treated spontaneously hypertensive rats (same doses), and nitro-L-arginine methyl ester for 3 weeks followed by untreated for 3 weeks. We examined renal function, blood pressure, histological features, oxidative stress markers, and mRNA expression in the renal cortex. RESULTS:Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats had higher blood pressure, proteinuria, and serum creatinine and lower creatinine clearance, urinary NO3/NO2 ratio, and urinary cGMP excretion compared with control spontaneously hypertensive rats (all Ps < 0.05). Nitro-L-arginine methyl ester-treated spontaneously hypertensive rats also had increased free radical metabolites and abnormal morphological findings with increased nicotinamide adenine dinucleotide phosphate oxidase activity, phosphorylation of myosin phosphatase targeting subunit-1, and mRNA expression of RhoA, RhoB, RhoC, collagen I and III, transforming growth factor-beta, nicotinamide adenine dinucleotide phosphate subunit, endothelial nitric oxide synthase, plasminogen activator inhibitor, and intercellular adhesion molecule-1 in the renal cortex compared with control spontaneously hypertensive rats. Long-term co-treatment with fasudil slightly improved these indices, but most of them were not statistically significant. Late fasudil treatment significantly improved kidney function, morphological changes, and alterations of mRNA expression in the renal cortex, although late untreated controls did not show any improvement. CONCLUSION:These results suggest that Rho-kinase inhibition partly reverses hypertensive glomerulosclerosis. The renoprotective effect of the Rho-kinase inhibitor may have multiple mechanisms including inhibition of extracellular matrix production, oxidative stress, adhesion molecule production, and antifibrinolysis.
journal_name
J Hypertensjournal_title
Journal of hypertensionauthors
Koshikawa S,Nishikimi T,Inaba C,Akimoto K,Matsuoka Hdoi
10.1097/HJH.0b013e328305086csubject
Has Abstractpub_date
2008-09-01 00:00:00pages
1837-48issue
9eissn
0263-6352issn
1473-5598pii
00004872-200809000-00019journal_volume
26pub_type
杂志文章abstract:OBJECTIVES:Endothelial dysfunction is associated to cardiovascular risk factors and predicts cardiovascular events. Peripheral arterial tonometry (PAT) is a novel noninvasive method to assess endothelial function. However, there is a paucity of data about its reproducibility. The aim of this study was to assess the fea...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328362d913
更新日期:2013-10-01 00:00:00
abstract:OBJECTIVE:To investigate the interrelationship between arrhythmias provoked by acute pressure changes, and the presence of left ventricular hypertrophy and electrolyte imbalances. DESIGN:An isolated working rat heart model was used in a prospective comparison of the effects of acute pressure changes in hypertensive an...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199202000-00010
更新日期:1992-02-01 00:00:00
abstract:OBJECTIVE:The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of endothelial nitric oxide synthase (eNOS) activity. When BH4 availability is limited, eNOS does not produce nitric oxide (NO) but instead generates superoxide. BH4 may reverse endothelial dysfunction due to cardiovascular...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000173520.13976.7d
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:To determine whether kidney stone disease (KSD) and hypertension (HTN) share a common familial component that is determined by a specific urinary biochemical abnormality. DESIGN:Familial aggregation study. PATIENTS:Two hundred and twelve KSD patients, aged 18-50 years, collected a 24-h urine sample to measu...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917121-00012
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:Angiotensin (Ang) II increases reactive oxygen species (ROS), decreases nitric oxide (NO) bioavailability and promotes cardiovascular remodeling. ROS have been identified as critical second messengers of the trophic responses by Ang II. In rats with Ang II-induced hypertension, we investigated the role of ROS...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000179513.71018.09
更新日期:2005-09-01 00:00:00
abstract:OBJECTIVE:To investigate the association between hypertension and musculoskeletal complaints among men and women selected by a population-based sample. METHODS:A cross-sectional study, with participants selected using a multistage sampling procedure and interviewed at home, was conducted to investigate the association...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e3283588268
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus is associated with an increased risk of hypertension, and cardiovascular and renal disease, and it has been recommended that management of hypertension should be more aggressive in presence than in absence of diabetes mellitus, but the matter is controversial at present. OBJECTIVES:...
journal_title:Journal of hypertension
pub_type: 杂志文章,meta分析,评审
doi:10.1097/HJH.0000000000001276
更新日期:2017-05-01 00:00:00
abstract:INTRODUCTION:The effectiveness of renal sympathetic denervation (RDN) as a treatment for therapy-resistant hypertension has been doubted as the Simplicity-HTN-3 trial was unable to show any treatment benefit over sham procedure. This might partly be explained by a high procedural variability in treatment with radiofreq...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/HJH.0000000000001301
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVE:To study 24-h ambulatory blood pressure (BP) and development of hypertension over four decades in women with childhood urinary tract infection (UTI) associated with renal damage. METHODS:A population-based group of 111 women was followed from their first UTI in childhood. The cohort was investigated at a med...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000234
更新日期:2014-08-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to identify the time of blood pressure (BP) drop in the orthostatic hypotension test, and to propose a realistic and appropriate duration in the orthostatic hypotension test. METHODS:A total of 879 consecutive patients (61-year-old and 44% women) with positive on the orthostatic...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002554
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVES:Increased central artery stiffness associates with cardiovascular disease. Among other factors, hypertension and aging are strong contributors to central artery stiffening, yet it has been difficult to separate their effects. Herein, we study isolated and combined effects of hypertension and aging on central...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002400
更新日期:2020-07-01 00:00:00
abstract:OBJECTIVE:Studies of experimental animals show glomerular hypertension to be important in the progression of glomerular disease. We evaluated this connection clinically by examining the relationship between glomerular hemodynamics and histological changes in patients with immunoglobulin (Ig)A nephropathy. METHODS:The ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-200018010-00015
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Nifedipine, an L-type calcium channel blocker, is widely used in the treatment of hypertension and coronary heart diseases, and also exhibits an antiplatelet activity. Activation of peroxisome proliferator-activated receptors (PPARs; α, β/δ, and γ) inhibits the platelet aggregation. Therefore, the purpose of ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000000007
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Orthostatic hypotension, postprandial hypotension, and carotid sinus hypersensitivity are hypotensive syndromes with high prevalence in older people. However, their pathophysiology and prognostic significance remain largely unknown. METHODS:In a retrospective cohort study of 313 consecutive patients visitin...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328352b9fd
更新日期:2012-06-01 00:00:00
abstract:OBJECTIVE:The new arterial hypertension guidelines by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) changed the definition of isolated diastolic hypertension (IDH). We assessed and compared in a Chinese population the IDH prevalence, newly defined by the 2017 ACC/AHA guidelines versus t...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000002659
更新日期:2020-10-06 00:00:00
abstract:OBJECTIVES:The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). METHODS:Sitagliptin (40 mg/kg twice daily) was given by...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e328341939d
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVE:In order to optimize cardiovascular risk assessment, we compared the association of common carotid artery intima-media thickness (CCA-IMT) with carotid and/or iliofemoral (C/IF) plaques according to the presence or absence of cardiovascular disease (CVD) and belonging to a high cardiovascular risk group. DES...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000052494.18130.80
更新日期:2003-04-01 00:00:00
abstract:OBJECTIVES:Night-time blood pressure (BP) - prognostically more important than circadian BP variability - has not been evaluated for quantitative associations with objective sleep quality in large populations. METHODS:The cross-sectional study measured actigraphic sleep parameters and night-time BP for two nights in 1...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001569
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVES:To evaluate the clinic and ambulatory blood pressure (BP)-lowering efficacy and safety of an aliskiren/amlodipine/hydrochlorothiazide (HCT) triple combination compared with the component dual combinations, in patients with moderate-to-severe hypertension. METHODS:This 8-week, double-blind, randomized, activ...
journal_title:Journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1097/HJH.0b013e328356b8ea
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:Coronary heart disease (CHD) risk factors have been consistently related to an increase in carotid intima-media thickness (IMT) in selected populations. However, few studies were population-based and furthermore little attention has been given to the influence of CHD risk factors on IMT in low-risk population...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199917060-00004
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:A recent editorial published by Verma and Strauss, entitled 'Angiotensin receptor blockers and myocardial infarction', examined, through a partial analysis of individual trials, the use of angiotensin receptor blockers (ARBs) in a variety of clinical settings. This editorial was reported widely in the lay pr...
journal_title:Journal of hypertension
pub_type: 杂志文章,meta分析,评审
doi:10.1097/01.hjh.0000194114.12228.16
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:In this randomized, double-blind, crossover study, the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) was compared following missed doses. Design and methods In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the ...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004872-200202000-00025
更新日期:2002-02-01 00:00:00
abstract:OBJECTIVE:Blood pressure (BP) increases both in winter and in the last trimester of pregnancy. Some interaction seems to exist between season and gestational age. The present study observed home BP values during pregnancy with adjustment for seasonal variation and gestational age. METHODS:We observed 10353 home BP mea...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0b013e32831364a7
更新日期:2008-12-01 00:00:00
abstract:OBJECTIVE:An excess morning blood pressure surge (MBPS) may portend an increased cardiovascular risk, but the mechanisms thereof have been little investigated. The link between MBPS, short-term blood pressure (BP) variability, and arterial stiffness has not been entirely defined. METHODS:In 602 consecutive untreated h...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/HJH.0000000000001153
更新日期:2017-02-01 00:00:00
abstract:OBJECTIVE:Inherited differences in renal function underlie the effect of high salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated by dietary sodium. METHODS:mRNA quantitation of both candidate genes implicated ...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000133719.94075.e2
更新日期:2004-08-01 00:00:00
abstract::An index of peripheral vascular resistance, derived from directly measured arterial pressure, has been developed and tested in an animal model. Assuming a mono-exponential character for diastole, the time constant for direct arterial pressure decay in the central aorta was obtained with high-fidelity recording techniq...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-198512000-00009
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVE:The repair process at the site of injury after percutaneous coronary intervention (PCI) is dominated by neointimal formation composed mainly of smooth muscle cells (SMC). Endothelin-1 (ET-1) is a powerful vasoconstrictor and SMC mitogen. Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/01.hjh.0000217854.97369.8c
更新日期:2006-04-01 00:00:00
abstract::Use of the aldosterone-to-renin ratio has controversially suggested that approximately 10% of hypertensives have primary aldosteronism, and most of these individuals are thought to have idiopathic hyperaldosteronism. The usual renin-angiotensin system control is intact in these individuals and is similar to that in lo...
journal_title:Journal of hypertension
pub_type: 杂志文章,评审
doi:10.1097/00004872-200201000-00003
更新日期:2002-01-01 00:00:00
abstract:OBJECTIVE:To introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment...
journal_title:Journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1097/00004872-199816110-00016
更新日期:1998-11-01 00:00:00
abstract:OBJECTIVE:The present study was designed to investigate the effect of nicardipine administration upon systolic blood pressure (SBP) and cardiac hypertrophy in spontaneously hypertensive rats (SHR). DESIGN:SBP, heart: and left ventricle: body weight ratios, the cross-sectional area of cardiocytes, and the ultrastructur...
journal_title:Journal of hypertension
pub_type: 杂志文章
doi:10.1097/00004872-199206000-00002
更新日期:1992-06-01 00:00:00