Abstract:
:Inhibition of calcineurin-mediated signaling in T lymphocytes is a major mechanism of cyclosporine A (CsA)-induced immunosuppression, and previous rat studies have suggested that inhibition of calcineurin-mediated signaling in central neuronal pools involved in blood pressure regulation plays an important role in causing acute CsA-induced hypertension. However, a central neural mechanism is difficult to reconcile with other data suggesting that CsA-induced hypertension is due to activation of renal and other subdiaphragmtic visceral afferents that reflexively increase efferent sympathetic nerve activity. Accordingly, we now have revised our hypothesis to suggest that CsA stimulates renal afferents by a calcineurin-dependent process. To test this new hypothesis, in anesthetized rats we recorded arterial pressure and multifiber afferent renal nerve activity from the cut distal end of the renal nerve before, during, and after intravenous infusion of either CsA (5 mg/kg over 20 min, n = 8), FK506 (0.15 mg/kg, n = 7), another potent calcineurin inhibitor that is structurally unrelated to CsA, or rapamycin (0.15 mg/kg, n = 4), a structural analog of FK506 that has no effect on calcineurin. We found that renal afferent discharge was increased markedly by intravenous FK506, as well as CsA, but unaffected by rapamycin (or vehicle), indicating calcineurin mediation. After infusion of either calcineurin inhibitor, afferent renal nerve activity remained elevated for up to 2 h, paralleling the prolonged increase in blood pressure. Thus, the major new conclusion of this study is that, in contrast to what has been assumed previously, calcineurin inhibitors enhance sympathetic neurotransmission by a novel action localized to visceral sensory nerve endings rather than to nerve cell bodies or central synapses. In the rat, calcineurin-dependent activation of renal afferents appears to be the primary mechanism producing the large blood-pressure-raising effect of CsA. Because the data suggest that the major side-effect of CsA and FK506--hypertension--is inexorably linked to calcineurin inhibition in extralymphoid tissue, development of agents that selectively inhibit calcineurin only in T lymphocytes could eliminate this important secondary form of hypertension.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Zhang W,Victor RGdoi
10.1016/s0895-7061(00)00288-0subject
Has Abstractpub_date
2000-09-01 00:00:00pages
999-1004issue
9eissn
0895-7061issn
1941-7225pii
S0895-7061(00)00288-0journal_volume
13pub_type
杂志文章abstract:BACKGROUND:Patients with chronic kidney disease (CKD) have a disproportionate risk of cardiovascular disease. This study was designed to assess the association between two noninvasive measures of cardiovascular risk, pulse wave analysis (PWA), and carotid intima-media thickness (IMT), in a cohort of CKD patients enroll...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.156
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension. The efficacy and safety of ramipril in adults has been proved; however, data on effectiveness of ramipril in children are few. The aim of the present study was to investigate the effect of ramipril on blood pressure (BP) ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.01.008
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:We reported that insulin modestly stimulates NAD(P)H oxidase activity in cultured rat vascular smooth muscle cells (VSMC) and synergistically stimulates enzyme activity with angiotensin II (Ang II), leading to synergistic stimulation of VSMC migration. The aim of this study was to determine the mechanism of ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.11.017
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:The X-linked angiotensin II type-2 receptor (AT2R) gene 1675G/A polymorphism is located in the short intron 1 of the AT2R gene within a sequence motif conforming to a splice branch site. AT2R is expressed in the human retina, but no previous study examined the association between retinal microvascular phenot...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.151
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not reaching obvious hypertension, suggesting that target organ damages are latently induced by slight BP rising. The goal of this study was to determine whether presence of subclinical myocardial damage can predict th...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpy008
更新日期:2018-04-13 00:00:00
abstract::Recently, we described a circulating hypertensive factor, present in the plasma of spontaneously hypertensive rats (SHR). This factor seems to be produced by the parathyroid gland but is not identical to parathyroid hormone (PTH). In view of these findings, we attempted to search for histological differences in parath...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/2.7.549
更新日期:1989-07-01 00:00:00
abstract:BACKGROUND:Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor family that has been implicated in cell differentiation and proliferation, glucose metabolism, macrophage development, and inflammatory responses. PPAR-gamma can be activated by a range of synthetic substances a...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2007.39
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Whether microvascular disease contributes to the development of left ventricular hypertrophy (LVH) is unclear. We examined the relationship of retinal microvascular signs with LVH in an African-American population. METHODS:A population-based, cross-sectional study of 1,439 middle-aged African-American parti...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2007.57
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Seventeen percent of youth in the United States are obese. Obesity has been linked to higher prevalence of hypertension. Past studies were limited by their size and conflicting results. The aim of this study was to analyze trends in adolescents' obesity between 1998 and 2011 and to evaluate the relationship ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv007
更新日期:2015-09-01 00:00:00
abstract::To evaluate the clinical importance of serum hepatocyte growth factor (HGF) concentration, we designed two clinical investigations. The first study analyzed the correlation between serum HGF concentration and clinical arterial stiffness or the vasodilator response to reactive hyperemia in hypertensive patients. The se...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(02)02274-4
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:The aim of this study was to clarify the response of endothelial connexins to hypertension and antihypertensive drugs. METHODS:Rats remained normotensive (group 1, N = 10) or were made hypertensive using N(omega)-nitro-L-arginine methyl ester (L-NAME) (groups 2 to 4, N = 10/group). Seven weeks later groups ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.08.020
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Progression of atherosclerosis with increased arterial stiffness is associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Compliance index (CI) derived from digital volume pulse (DVP), measuring the relationship between volume and pressure changes in ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2010.266
更新日期:2011-05-01 00:00:00
abstract:BACKGROUND:Aortic pulse wave velocity (PWV) is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end-stage renal disease receiving hemodialysis. Little data exist char...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.240
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:Calcium channel blockers such as amlodipine are effective antihypertensive agents. In this study we investigated the effects of amlodipine on vascular oxidative stress, expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1), and endothelial function in angiotensin (Ang) II-infused ra...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2003.09.007
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:Marinobufagenin (MBG) is an endogenous Na/K-ATPase inhibitor, a natriuretic and a vasoconstrictor. MBG is implicated in salt-sensitive hypertension, cardiac hypertrophy, and initiate the pro-fibrotic signaling. Previously it was demonstrated that immunoneutralization of an endogenous MBG by 3E9 anti-MBG-anti...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv155
更新日期:2016-05-01 00:00:00
abstract:BACKGROUND:Complement factor H (CFH) is a plasma protein that is essential in the regulation of the alternative complement pathway and has been implicated as taking part in complement inhibition in atherogenesis. We evaluated the association of the Y402H polymorphism with incident coronary heart disease (CHD), incident...
journal_title:American journal of hypertension
pub_type: 杂志文章,多中心研究
doi:10.1038/ajh.2007.81
更新日期:2008-05-01 00:00:00
abstract::Atherosclerosis is increasingly recognized as an inflammatory vascular disease, and high blood pressure (BP) has been suggested to exert a proinflammatory action. Whether plasma viscosity (PV), a major determinant of blood flow in microcirculation and a marker of systemic inflammation and cardiovascular risk, is incre...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.01.014
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Inadequately treated hypertension (HTN) leads to considerable morbidity and mortality. Despite many treatment options, blood pressure (BP) control is suboptimal. Missed opportunities due to the growing complexity of primary care office visits contribute. Electronic health records (EHRs) offer best practice a...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpy155
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity in hypertension. Current evidence suggests a contribution to LVH of plasma aldosterone levels that are inappropriately elevated for the salt status. The aim of this study was to investigate whether inappropriate mod...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv104
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:All renin arises from prorenin. The proportion of renin relative to prorenin could influence overall renin-angiotensin-aldosterone activity. We sought to determine whether prorenin levels were related to extracellular volume, as reflected by the levels of plasma renin activity (PRA), and to aldosterone. MET...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2012.83
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing EC...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu268
更新日期:2015-08-01 00:00:00
abstract::Hyperinsulinemia and dyslipidemia are known to be associated with essential hypertension but their role in pregnancy-induced hypertension remains unclear. We performed a case-control study comparing cholesterol, insulin, and glucose levels in the early third trimester of pregnancy among 31 women who developed pregnanc...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(98)00258-1
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND:The independent prognostic value of daytime and night-time blood pressure (BP) variability estimated by noninvasive 24-h BP monitoring is unclear. METHODS:We followed 2649 initially untreated subjects with essential hypertension for up to 16 years (mean, 6). Variability of BP was estimated by the standard d...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.07.017
更新日期:2007-02-01 00:00:00
abstract:BACKGROUND:The independent prognostic significance of the metabolic syndrome (MetS) in the elderly is not yet clear. We investigated the association between MetS and cardiovascular risk (composite endpoint of stroke and coronary events) in elderly treated hypertensive patients. METHODS:Cardiovascular outcome was evalu...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpv121
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:The ratio of urinary concentrations of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone [(THF + ATHF)/THE] reflects the activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11BHSD2), which converts cortisol to cortisone in the kidney and thereby protects the mineralocortico...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(03)00981-6
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, ha...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpaa006
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Increased short-term blood pressure (BP) variability (BPV) in hemodialysis is associated with increased cardiovascular and all-cause mortality. Studies on the impact of BP-lowering interventions on BPV are scarce. This study examined the effect of dry-weight reduction with a lung ultrasound-guided strategy o...
journal_title:American journal of hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/ajh/hpz064
更新日期:2019-07-17 00:00:00
abstract::We investigated the effects of 17 beta-estradiol (beta E2), alpha-estradiol (alpha E2), and progesterone (P) on baseline and vasopressin (AVP)-induced [Ca2+]i in human platelets obtained from healthy male and female volunteers. Platelets were treated with beta E2, alpha E2, P, or ethanol vehicle for 30 min at 37 degre...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(94)00168-B
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:The expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is upregulated in spontaneously hypertensive rat (SHR). We investigated whether expression of NKCC1 is epigenetically regulated during postnatal development of hypertension. METHODS:The mesenteric arteries from 5-, 10-, and 18-week-old Wistar-Kyoto...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.136
更新日期:2011-12-01 00:00:00
abstract::We have previously reported that young, primigravid, African-American women who developed preeclampsia exhibited insulin resistance (elevated fasting insulin:glucose ratios) and abnormal intracellular free calcium ([Ca2+]i) metabolism as early as the second trimester of pregnancy. To determine if these abnormalities p...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/6.4.302
更新日期:1993-04-01 00:00:00