Abstract:
BACKGROUND:Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. METHODS:ZDF rats were treated with vehicle or AZL-M for 8 weeks. Zucker diabetic lean (ZDL) rats were used as controls. Urine and plasma samples were collected for biochemical analysis, and kidney tissues were used for histopathological and immunohistopathological examination at the end of the 8-week protocol. RESULTS:ZDF rats were diabetic with hyperglycemia and impaired glucose tolerance, and AZL-M ameliorated the diabetic phenotype. ZDF rats were hypertensive compared with ZDL rats (181±6 vs. 129±7mm Hg), and AZL-M decreased blood pressure in ZDF rats (116±7mm Hg). In ZDF rats, there was marked renal damage with elevated proteinuria, albuminuria, nephrinuria, 2-4-fold higher tubular cast formation, and glomerular injury compared with ZDL rats. AZL-M treatment reduced renal damage in ZDF rats. ZDF rats demonstrated renal inflammation and oxidative stress with elevated urinary monocyte chemoattractant protein 1 excretion, renal infiltration of macrophages, and elevated kidney malondialdehyde levels. AZL-M reduced oxidative stress and inflammation in ZDF rats. CONCLUSIONS:Overall, we demonstrate that AZL-M attenuates kidney damage in type 2 diabetes. We further demonstrate that anti-inflammatory and antioxidative activities of AZL-M contribute to its kidney protective action.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Hye Khan MA,Neckář J,Haines J,Imig JDdoi
10.1093/ajh/hpu016subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1087-95issue
8eissn
0895-7061issn
1941-7225pii
hpu016journal_volume
27pub_type
杂志文章abstract::The purpose of the present study was to determine whether the physiological dopamine prodrug, L-dopa, could suppress streptozotocin-induced diabetic glomerular hyperfiltration, and thus prevent further evolution of the diabetic nephropathy. Male Wistar rats treated with streptozotocin (60 mg/kg, intravenously) rapidly...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.6.72s
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:Retinal abnormalities, particularly arteriolar narrowing, are powerful predictors of cardiovascular events. The precision of internists and ophthalmologists in the assessment of retinal vessels widths has been disputed but not evaluated against a technology of edge detection. METHODS:Fifty-two patients with...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.10.012
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND:Population-level sociologic studies have suggested that adverse societal conditions may affect fetal viability in a sex-specific manner and thereby modify the ratio of male vs. female babies. This concept suggests that there may exist certain physiologic features in a woman that relate to her likelihood of d...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpw165
更新日期:2017-04-01 00:00:00
abstract::In order to evaluate the effects of atrial natriuretic factor (ANF) infusion on plasma insulin (IRI) in hypertension, 32 essential hypertensives (aged 40 to 62 years) were studied. After 1 week of pharmacologic washout under normal sodium intake (120 mEq of Na+/day), patients were randomly assigned to receive either A...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/ajh/4.11.880
更新日期:1991-11-01 00:00:00
abstract::Previous studies showed that alpha 2-adrenergic receptors and imidazoline-guanidinium receptive sites (IGRS) are colocalized in rabbit and human renal proximal tubule. In the present study we investigated the localization of these two binding sites in the renal medulla from human kidney. Binding studies performed with...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/5.4.69s
更新日期:1992-04-01 00:00:00
abstract::Components of the kallikrein kinin system have been associated with the pathophysiology of hypertension in animal and human studies. In this study, we examined the distribution of four different polymorphisms of the kinin B1 and B2 receptor genes in a population of 120 normotensive and 77 hypertensive African-American...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(00)01215-2
更新日期:2000-12-01 00:00:00
abstract::The relation between 24-h ambulatory blood pressure monitoring and echocardiographic left ventricular (LV) anatomy and function was examined in 30 young, normotensive offspring (16 men, 14 women) of hypertensive, parents and in 20 offspring (12 men, 8 women) of normotensive parents, comparable for age, clinical blood ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/6.2.114
更新日期:1993-02-01 00:00:00
abstract::The role of an endogenous sodium pump inhibitor in the pathogenesis of hypertension has been reported in several papers. Unfortunately, because of the unknown structure and lack of biochemical characterization, some discrepancies have arisen. In this study we report a method to obtain extracts from human plasma that a...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/1.3.56s
更新日期:1988-07-01 00:00:00
abstract::The role of renal sympathetic nerve activity (RSNA) in the maintenance phase of essential hypertension has not yet been clearly defined. Renal function and mean arterial pressure (MAP) were studied in four Yucatan miniature swine (YMS) with established DOCA hypertension prior to and for 3 weeks after surgical renal de...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.1.62
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:In middle-aged and elderly populations, circulating natriuretic peptide concentrations are negatively associated with several components of the metabolic syndrome. Whether these negative associations are also present in healthy adolescents and young adults from the general population are unknown. METHODS:In...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpx026
更新日期:2017-06-01 00:00:00
abstract::The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether treatment with an angiotensin II (ANGII) subtype-1 receptor antagonist delays the onset of NIDDM and attenuates diabetic nephropathy in the OLETF rat. OLETF rats fed a re...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(98)00276-3
更新日期:1999-01-01 00:00:00
abstract::Onset of diabetes increases plasma renin activity (PRA) and glomerular filtration rate (GFR), but blood pressure (BP) is normal. In this study, a 70% surgical reduction in kidney mass (RK) was used to decrease baseline GFR and to prevent hyperfiltration during diabetes, and angiotensin converting enzyme inhibitors (AC...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.05.012
更新日期:2006-12-01 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::The purpose of this study was to determine whether antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril would alter cell Na+ transport kinetics, metabolic parameters associated with insulin resistance, or both in young adults with mild hypertension. Sixteen young adults (mean age 29 +/-...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(95)00018-K
更新日期:1995-05-01 00:00:00
abstract::Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension-at least with diuretics and beta-blockers-may more effectively protect ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(97)00496-2
更新日期:1998-03-01 00:00:00
abstract::Twenty-four hour blood pressure exposure and circadian blood pressure variability may be important predictors of hypertensive end-organ damage. Since sleep is a major determinant of circadian blood pressure decline, day/night blood pressure changes may be affected by sleep intervals. The current study compares 24-h bl...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1016/0895-7061(95)00196-V
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND:We examined the associations of epithelial sodium channel (ENaC) genes with blood pressure (BP) changes and hypertension incidence in a longitudinal family study. METHODS:A total of 2,755 Han Chinese participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) baseline examination were eli...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu060
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Preeclampsia is a human pregnancy-associated syndrome associated with hypertension, proteinuria, and endothelial dysfunction. We tested whether increased reactive oxygen species (superoxide and peroxynitrite) production and decreased bioavailability of the endothelial nitric oxide (NO) synthase (eNOS) cofact...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2007.08.007
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:This study evaluated the effect of chronic sucrose feeding on hemodynamic parameters and renal sympathetic nervous activity. In addition, angiotensin I, II, and 1-7 levels were determined in plasma, heart, kidney, and the epididymal adipose tissue. METHODS:Male Wistar rats were treated for 30 days with 20% ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2007.01.014
更新日期:2007-06-01 00:00:00
abstract::The objective of the present study was to determine the relationship between plasma renin levels, and the development of hypertension and cardiac hypertrophy in TGR (mREN2)27 hypertensive rats. Systolic blood pressure and left ventricular mass index (LVMI) were measured in transgenic heterozygote and normotensive Spra...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(95)00254-5
更新日期:1995-12-01 00:00:00
abstract::The sensitivity and specificity of screening and diagnostic studies for renovascular hypertension has been the focus of debate and disappointment for many years. The use of these studies has been further restricted by the insistence of clinicians that studies provide visual identification of the anatomy of the renal v...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/4.12.663s
更新日期:1991-12-01 00:00:00
abstract:BACKGROUND:Normal pregnancy is characterized by a decrease in peripheral resistance and generalized vasodilation resulting in plasma volume expansion, which is associated with intrauterine growth. Stiffness of the arterial system may be a measure of the degree of plasma volume expansion. Pulse wave velocity (PWV), meas...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.10.020
更新日期:2005-03-01 00:00:00
abstract::Echocardiography (ECHO) is useful to document changes in left ventricular mass (LVM) in groups of patients, but may be too variable for use in the individual patient. Magnetic resonance imaging (MRI) may be a more precise and reliable method to quantify the mass of the left ventricule. This study reports the accuracy,...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(94)00178-E
更新日期:1995-03-01 00:00:00
abstract::The results of ambulatory blood pressure monitoring (ABPM) in children after kidney transplant were analyzed to ascertain any alteration in circadian BP profile, degree of hypertension, and efficacy of therapy. The data were also compared with casual BP data and left ventricular mass index (LVMI). We have examined 30 ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(97)00484-6
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND:The effect of age on the augmentation index (AI) differs between young adults and the elderly, and the AI reaches a plateau after the age of 60 years. We examined whether the effects of age and an elevation in blood pressure on the AI differ between young adults and the elderly, between subjects with and wit...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu082
更新日期:2014-12-01 00:00:00
abstract::Evidence is presented that bradykinin inhibits norepinephrine efflux from sympathetic nerves innervating canine mesenteric and pulmonary arteries, in part, by releasing endothelium-derived relaxing factor (EDRF) from the vascular endothelium. Moreover, in the absence of vascular endothelium, bradykinin also inhibits n...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/4.5.464
更新日期:1991-05-01 00:00:00
abstract::The different modes of antihypertensive action of beta-adrenoceptor blocking drugs are reviewed with a special emphasis on renal mechanisms of action. Beta-adrenoceptors occur in the kidney at the level of the juxtaglomerular and tubular cells. Direct intrarenal effects of beta-blockers include the decrease in renin r...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/2.11.237s
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND:Hypertension is a significant global public health challenge. Low-grade inflammation is known to facilitate the development of essential hypertension and target-organ hypertensive damage. Neutrophil to lymphocyte ratio (NLR) is a simple and reliable indicator of inflammation that may also be useful in the pr...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv034
更新日期:2015-11-01 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:BACKGROUND:Noninvasive applanation tonometry (APT) is useful to assess aortic stiffness and pulse wave reflection. Moreover, APT can predict outcome in many conditions such as arterial hypertension. In this study, we test whether APT measurements relate to progression of aortic disease in Marfan syndrome (MFS). METHOD...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.115
更新日期:2009-09-01 00:00:00