Cardioprotective Effects of Paricalcitol Alone and in Combination With FGF23 Receptor Inhibition in Chronic Renal Failure: Experimental and Clinical Studies.


BACKGROUND:In uremic animals, vitamin D receptor (VDR) agonists like paricalcitol (Pc) attenuate cardiac hypertrophy, but this effect has not been replicated consistently in humans with chronic kidney disease. Elevated fibroblast growth factor 23 (FGF23) levels cause cardiac hypertrophy with activation of the myocardial calcineurin/nuclear factor of activated T cell (NFAT) axis and may antagonize the cardioprotective effects of VDR agonist therapy. We hypothesized that the effectiveness of Pc may depend on the prevailing circulating levels of FGF23 and could be potentiated by the combined administration of a pan-FGF23 receptor (FGFR) blocker agent (PD173074). METHODS:In rats with 5/6 nephrectomy treated with Pc or PD173074 or both agents concurrently, myocardial mRNA expression of renin-angiotensin system, VDR, FGFR4, and calcineurin/NFAT target genes was determined. In adolescents on hemodialysis, we analyzed sequential echocardiograms, blood pressures and serial FGF23 measurements, and their relations to the cumulative administered dose of parenteral Pc. RESULTS:The ratio of Pc dose/plasma levels of FGF23 correlated inversely (P < 0.005) with the cardiac mass in uremic rats and in hemodialysis patients, independently of hypertension. Despite persistently elevated FGF23 levels and myocardial FGFR4 activation, Pc suppressed upregulated myocardial calcineurin/NFAT target genes, and the effects were amplified by coadministration of PD173074. CONCLUSIONS:The beneficial effects of Pc on uremic cardiac hypertrophy are counterbalanced by the increased FGF23 levels. Blockade of FGF23-mediated signaling increased the Pc-induced suppression of the myocardial calcineurin/NFAT system. Higher doses of Pc should be considered in the treatment of patients with uremic cardiomyopathy.


Am J Hypertens


Czaya B,Seeherunvong W,Singh S,Yanucil C,Ruiz P,Quiroz Y,Grabner A,Katsoufis C,Swaminathan S,Abitbol C,Rodriguez-Iturbe B,Faul C,Freundlich M




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2019-01-01 00:00:00














  • Ambulatory blood pressure monitoring in offspring of hypertensive patients. Relation to left ventricular structure and function.

    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


    authors: Galderisi M,Celentano A,Tammaro P,Mureddu GF,Garofalo M,de Simone G,de Divitiis O

    更新日期:1993-02-01 00:00:00

  • Development of structural vascular changes with subpressor angiotensin II administration in rats.

    abstract::We investigated whether the slow pressor action of small doses of angiotensin II (ANG II) administered to rats was accompanied by the development of structural vascular changes. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 7 to 10 days or 6 weeks, or 100 ng/kg/min for...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Simon G,Cserep G,Limas C

    更新日期:1995-01-01 00:00:00

  • Effects of nabumetone, celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors.

    abstract::Nonsteroidal anti-inflammatory drugs interfere with certain antihypertensive therapies. In a double-blind study, 385 hypertensive patients stabilized on an angiotensin converting enzyme inhibitor were treated with nabumetone, celecoxib, ibuprofen, or placebo for 4 weeks. Ibuprofen caused significantly greater increase...

    journal_title:American journal of hypertension

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验


    authors: Palmer R,Weiss R,Zusman RM,Haig A,Flavin S,MacDonald B

    更新日期:2003-02-01 00:00:00

  • Epicardial coronary artery size in hypertensive and physiologic left ventricular hypertrophy.

    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


    authors: Kozakova M,Paterni M,Bartolomucci F,Morizzo C,Rossi G,Galetta F,Palombo C

    更新日期:2007-03-01 00:00:00

  • Sodium retention and volume expansion as mechanisms.

    abstract::After nephrectomy, the level of arterial pressure is determined by the permitted degree of fluid volume expansion. With kidneys present, the fundamental requirement for fluid volume homeostasis is met by maintaining the balance between sodium and water intake and output. When one-kidney, one-clip (1-K,1-C) hypertensio...

    journal_title:American journal of hypertension

    pub_type: 杂志文章,评审


    authors: Ledingham JM

    更新日期:1991-10-01 00:00:00

  • Hypertension and arterial stiffness: the Atherosclerosis Risk in Communities Study. ARIC Investigators.

    abstract::Our objective was to describe the relationship of arterial stiffness and hypertension in a large, population-based sample of men and women. Hypertension-related increases in arterial stiffness may reflect the distending pressure and/or structural alterations in the artery. Included were 10,712 participants, ages 45 to...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Arnett DK,Boland LL,Evans GW,Riley W,Barnes R,Tyroler HA,Heiss G

    更新日期:2000-04-01 00:00:00

  • Body mass index is not independently associated with increased aortic stiffness in a Brazilian population.

    abstract:BACKGROUND:Obesity has been described as a predictor of cardiovascular mortality, and some studies have reported an association with obesity and increased aortic stiffness. Other studies have not identified obesity to be an independent risk factor. Therefore, the purpose of our study was to determine the association be...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Rodrigues SL,Baldo MP,Lani L,Nogueira L,Mill JG,Sa Cunha Rd

    更新日期:2012-10-01 00:00:00

  • Birth measurements, family history, and environmental factors associated with later-life hypertensive status.

    abstract:BACKGROUND:This birth cohort study was conducted to investigate the contribution of prenatal and antenatal environmental exposures to later-life hypertensive status. METHODS:Two thousand five hundred and three individuals born in 1921-1954 at the Peking Union Medical College Hospital (PUMCH) were targeted; 2,081 (83.1...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Chen X,Zhang ZX,George LK,Wang ZS,Fan ZJ,Xu T,Zhou XL,Han SM,Wen HB,Zeng Y

    更新日期:2012-04-01 00:00:00

  • Triacylglycerol molecular species are depleted to different extents in the myocardium of spontaneously hypertensive rats fed two oleic acid-rich oils.

    abstract:BACKGROUND:During the development of hypertension, glucose replaces triacylglycerols (TG) as the main energy source for the myocardium. However, there are no available studies investigating the TG molecular species composition of the myocardium in the spontaneously hypertensive rat (SHR). The objective of this study wa...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Perona JS,Ruiz-Gutierrez V

    更新日期:2005-01-01 00:00:00

  • Maternal endothelial progenitor colony-forming units with macrophage characteristics are reduced in preeclampsia.

    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


    authors: Lin C,Rajakumar A,Plymire DA,Verma V,Markovic N,Hubel CA

    更新日期:2009-09-01 00:00:00

  • Antihypertensive Drug Therapy. The effect of JNC criteria on prescribing patterns and patient status through the first year.

    abstract::This study was designed to evaluate the impact of the protocol-driven antihypertensive therapy on outcomes guided by the Joint National Committee (JNC) on Detection, Evaluation, and Treatment of high blood pressure. In a systematic hypertension control program for union employees conducted in New York City, untreated ...

    journal_title:American journal of hypertension

    pub_type: 临床试验,杂志文章


    authors: Alderman MH,Madhavan S,Cohen H

    更新日期:1996-05-01 00:00:00

  • High K diets markedly reduce atherosclerotic cholesterol ester deposition in aortas of rats with hypercholesterolemia and hypertension.

    abstract::High K diets prevent hypertensive endothelial injury and intimal thickening. Cholesterol esters often deposit during hypercholesterolemia. Would a high K diet influence cholesterol ester deposits? In a normal rat on a normal diet, no cholesterol esters are detected in the aorta. Stroke prone SHR rats were fed for 3 mo...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Tobian L,Jahner TM,Johnson MA

    更新日期:1990-02-01 00:00:00

  • Hypotensive effects of the lipoxygenase inhibitor phenidone in two-kidney, one clip Goldblatt hypertension.

    abstract::This study examined the role of the lipoxygenase (LO) pathway in the maintenance of hypertension in rats with two-kidney, one clip (2K,1C) Goldblatt hypertension. A single dose of the lipoxygenase blocker phenidone was injected intraperitoneally to 2K,1C rats during the early phase (14 days) of the development of hype...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Nozawa K,Tuck ML,Golub M,Eggena P,Nadler J,Stern N

    更新日期:1989-11-01 00:00:00

  • Effect of dietary sodium on insulin sensitivity in older, obese, sedentary hypertensives.

    abstract::Increased dietary sodium intake has been associated with an increase in blood pressure as well as a decrease in insulin-mediated glucose disposal in young healthy adults. The purpose of this study was to determine whether dietary sodium intake is associated with changes in oral glucose tolerance, insulin sensitivity, ...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Dengel DR,Mayuga RS,Kairis GM,Goldberg AP,Weir MR

    更新日期:1997-09-01 00:00:00

  • Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension.

    abstract::Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in pati...

    journal_title:American journal of hypertension

    pub_type: 杂志文章,评审


    authors: Schifter S,Krusell LR,Sehested J

    更新日期:1991-07-01 00:00:00

  • Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review).

    abstract:BACKGROUND:The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids. METHODS:Studies randomizing persons to low-sodium an...

    journal_title:American journal of hypertension

    pub_type: 杂志文章,meta分析,评审


    authors: Graudal NA,Hubeck-Graudal T,Jürgens G

    更新日期:2012-01-01 00:00:00

  • Cardioprotective effects of pitavastatin on cardiac performance and remodeling in failing rat hearts.

    abstract:BACKGROUND:Activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling by statins increases the activity of endothelial nitric oxide synthase (eNOS). We investigate whether statins (pitavastatin) improve cardiac function and remodeling via eNOS production associated with the PI3K-Akt signaling pathway, Rho-kinase ...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Kobayashi N,Takeshima H,Fukushima H,Koguchi W,Mamada Y,Hirata H,Machida Y,Shinoda M,Suzuki N,Yokotsuka F,Tabei K,Matsuoka H

    更新日期:2009-02-01 00:00:00

  • The Case for Low Blood Pressure Targets.

    abstract::The "totality" of hypertension clinical trial endpoint data has shown that the absolute benefit of pharmacological blood pressure (BP) lowering is directly related to the BP level and baseline cardiovascular risk, albeit with attenuation of the relative risk reduction per unit of BP lowering in patients with diabetes ...

    journal_title:American journal of hypertension

    pub_type: 杂志文章,评审


    authors: Flack JM,Nolasco C,Levy P

    更新日期:2017-01-01 00:00:00

  • Effectiveness of a Best Practice Alerts at Improving Hypertension Control.

    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


    authors: Swedlund M,Norton D,Birstler J,Chen G,Cruz L,Hanrahan L

    更新日期:2019-01-01 00:00:00

  • Elevated myocardial repolarization lability and arterial baroreflex dysfunction in healthy individuals with nondipping blood pressure pattern.

    abstract:BACKGROUND:The "nondipping" pattern (NDP) of blood pressure, characterized by the absence of the reduction in blood pressure (BP) that typically takes place during the night time, has been associated with elevated cardiovascular morbidity, including stroke, myocardial infarction, and sudden cardiac-related death. In va...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Myredal A,Friberg P,Johansson M

    更新日期:2010-03-01 00:00:00

  • Role of neurohumoral systems for pressure induced left ventricular hypertrophy in experimental supravalvular aortic stenosis in rats.

    abstract::We studied the role of the sympathetic nervous system and the renin angiotensin system for pressure induced left ventricular hypertrophy (LVH) in 135 rats with experimental supravalvular aortic stenosis (AS). We induced this condition by a silver clip on the ascending aorta, when body weight (BW) was 90 to 100 g. Symp...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Kromer EP,Elsner D,Riegger GA

    更新日期:1991-06-01 00:00:00

  • Predictive value for mortality of the double product at rest obtained by home blood pressure measurement: the Ohasama study.

    abstract:BACKGROUND:To clarify whether the double product (DP) (product of systolic blood pressure (SBP) and pulse rate (PR)) at rest based on home blood pressure (HBP) measurement has prognostic value for mortality. METHODS:HBP data of 2,583 participants from a Japanese general population (40% men) ≥35 years of age (mean, 59 ...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Inoue R,Ohkubo T,Kikuya M,Metoki H,Asayama K,Kanno A,Obara T,Hirose T,Hara A,Hoshi H,Totsune K,Satoh H,Kondo Y,Imai Y

    更新日期:2012-05-01 00:00:00

  • Identification of a functional Na+/Mg2+ exchanger in human trophoblast cells.

    abstract:BACKGROUND:Ionized magnesium levels are elevated in fetal blood compared with maternal blood, suggesting that the placenta may possess an active transport mechanism for magnesium. In the present study, we sought to determine the existence of an active transport mechanism for magnesium in the placenta using cultured tro...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Standley PR,Standley CA

    更新日期:2002-06-01 00:00:00

  • Ethnic differences in the identification of left ventricular hypertrophy in the hypertensive patient.

    abstract::Left ventricular hypertrophy (LVH) is more prevalent in black than white hypertensives, but this difference is greater when identified by electrocardiography (ECG) than by echocardiography. We evaluated the proposal that current ECG criteria for LVH are less specific, and therefore, less useful, in blacks than whites....

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Chapman JN,Mayet J,Chang CL,Foale RA,Thom SA,Poulter NR

    更新日期:1999-05-01 00:00:00

  • Role for granulocyte colony stimulating factor in angiotensin II-induced neutrophil recruitment and cardiac fibrosis in mice.

    abstract:BACKGROUND:Granulocyte colony stimulating factor (G-CSF) is a key mediator of neutrophil infiltration and is profibrotic in the liver, lung, and infarcted heart, but its roles in angiotensin II (Ang II)-induced hypertension and cardiac remodeling have not been fully determined. Thus, we sought to investigate the causal...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Jiang HM,Wang HX,Yang H,Zeng XJ,Tang CS,Du J,Li HH

    更新日期:2013-10-01 00:00:00

  • The sympathetic drive after acute myocardial infarction in hypertensive patients.

    abstract:BACKGROUND:Sympathetic activation occurs in hypertension (HT) and after acute myocardial infarction (AMI) and is related to greater cardiovascular risk. Also, AMI in patients with HT (AMI-HT) carries greater risk than that in normal subjects (AMI-NT). We therefore planned to determine whether the sympathetic activation...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Hogarth AJ,Mackintosh AF,Mary DA

    更新日期:2006-10-01 00:00:00

  • Physical Activity Is Associated With Reduced Left Ventricular Mass in Obese and Hypertensive African Americans.

    abstract:BACKGROUND:Physical activity (PA) has been associated with decreased left ventricular (LV) hypertrophy in previous studies. However, little is known about the relationship between PA and LV structure and factors which influence this relationship among African Americans. METHODS:We evaluated 1,300 African Americans wit...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Kamimura D,Loprinzi PD,Wang W,Suzuki T,Butler KR,Mosley TH,Hall ME

    更新日期:2017-06-01 00:00:00

  • Renovascular hypertension induces myocardial mitochondrial damage, contributing to cardiac injury and dysfunction in pigs with metabolic syndrome.

    abstract:BACKGROUND:Subjects with renovascular hypertension (RVH) often manifest with metabolic syndrome (MetS) as well. Coexisting MetS and hypertension increases cardiovascular morbidity and mortality, but the mechanisms underlying cardiac injury remain unknown. We hypothesized that superimposition of MetS induces myocardial ...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Aghajani Nargesi A,Farah MC,Zhu XY,Zhang L,Tang H,Jordan KL,Saadiq IM,Lerman A,Lerman LO,Eirin A

    更新日期:2020-12-05 00:00:00

  • Hemodynamics and Vascular Hypertrophy in African Americans and Caucasians With High Blood Pressure.

    abstract:BACKGROUND:Hypertension in African Americans is characterized by greater systemic vascular resistance (SVR) compared with Caucasian Americans, but the responsible mechanisms are not known. The present study sought to determine if peripheral vascular hypertrophy is a potential mechanism contributing to elevated SVR in A...

    journal_title:American journal of hypertension

    pub_type: 杂志文章


    authors: Hill LK,Sherwood A,Blumenthal JA,Hinderliter AL

    更新日期:2016-12-01 00:00:00

  • Endothelium-derived and intraneuronal nitric oxide-dependent inhibition of norepinephrine efflux from sympathetic nerves by bradykinin.

    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


    authors: Greenberg SS,Peevy K,Tanaka TP

    更新日期:1991-05-01 00:00:00