Impaired L-arginine uptake but not arginase contributes to endothelial dysfunction in rats with chronic kidney disease.

Abstract:

:Reduced nitric oxide bioavailability contributes to increased cardiovascular disease risk in patients with chronic kidney disease (CKD). Arginase has been implicated as a potential therapeutic target to treat vascular dysfunction by improving substrate availability for endothelial nitric oxide synthase. The purpose of this study was to determine if arginase contributes to endothelial dysfunction in the 5/6 ablation infarction (AI) rat model of CKD. Endothelium-dependent relaxation of aortic rings to acetylcholine was significantly impaired in AI animals versus sham after 8 weeks and was not improved by arginase inhibition (S-(2-Boronoethyl)-L-cysteine hydrochloride) alone or in combination with L-arginine. Additionally, scavenging of superoxide (Tempol, Tempol + L-arginine, Tempol + L-arginine + S-(2-Boronoethyl)-L-cysteine hydrochloride) was not effective, suggesting that a mechanism independent of oxidative stress contributes to endothelium-dependent relaxation in moderate to severe CKD. Aortic uptake of radiolabeled L-arginine was attenuated in AI animals and was associated with a reduced expression of the L-arginine transporter CAT-1. These data suggest that arginase does not contribute to endothelial dysfunction in CKD; however, impaired L-arginine transport may play an important role in diminishing substrate availability for nitric oxide production leading to endothelial dysfunction.

journal_name

J Cardiovasc Pharmacol

authors

Martens CR,Kuczmarski JM,Lennon-Edwards S,Edwards DG

doi

10.1097/FJC.0000000000000022

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

40-8

issue

1

eissn

0160-2446

issn

1533-4023

journal_volume

63

pub_type

杂志文章
  • Intravenous adrenomedullin in myocardial function and energy metabolism in patients after myocardial infarction.

    abstract::This study investigated the effects of adrenomedullin on left ventricular myocardial contraction and relaxation, coronary blood flow, and myocardial oxygen consumption in comparison with those of atrial natriuretic peptide (ANP). Fourteen patients who had had myocardial infarctions were randomly assigned to receive IV...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-200205000-00017

    authors: Nagaya N,Goto Y,Satoh T,Sumida H,Kojima S,Miyatake K,Kangawa K

    更新日期:2002-05-01 00:00:00

  • Long-term effects of felodipine on blood pressure and renal hemodynamics in severe hypertension.

    abstract::Felodipine, a dihydropyridine calcium antagonist, was used to treat eight patients with severe uncontrolled hypertension: five had essential hypertension, two had renovascular disease, and one chronic pyelonephritis. Mean blood pressure (BP) was 221 +/- 14/120 +/- 4 mm Hg despite treatment with three or more antihyper...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199015004-00032

    authors: Herlitz H,Granérus G,Aurell M

    更新日期:1990-01-01 00:00:00

  • Effects of angiotensin II AT1-receptor blockade on coronary dynamics, function, and structure in postischemic heart failure in rats.

    abstract::Angiotensin II AT1-receptor blockers (AT1-s) prolong survival in experimental postischemic (coronary artery ligation) heart failure (CHF) in rats. The goal of this study was to investigate whether potential beneficial effects of short- and/or long-term treatment with AT1-s on coronary dynamics, function, and structure...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200009000-00008

    authors: Gervais M,Fornes P,Richer C,Nisato D,Giudicelli JF

    更新日期:2000-09-01 00:00:00

  • Antiarrhythmic activity of amiloride: mechanisms.

    abstract::We have previously shown that amiloride suppresses the induction of sustained ventricular tachycardia both in dogs late following myocardial infarction and in patients. In those studies the only electrophysiologic correlate of amiloride's antiarrhythmic activity observed was prolongation of ventricular effective refra...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199106000-00004

    authors: Duff HJ,Brown CE,Cragoe EJ,Rahmberg M

    更新日期:1991-06-01 00:00:00

  • Cardioprotective effect of zofenopril in perfused rat heart subjected to ischemia and reperfusion.

    abstract::We investigated the effect of different ACE inhibitors on tissue injury in isolated rat hearts subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Zofenoprilat (1-100 microM), but not enalaprilat or lisinopril, significantly reduced infarct size, as estimated on the basis of triphenyltetrazoliu...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200402000-00020

    authors: Frascarelli S,Ghelardoni S,Ronca-Testoni S,Zucchi R

    更新日期:2004-02-01 00:00:00

  • Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates.

    abstract::Platelet GPIIb/IIIa antagonists are not only used to prevent platelet aggregation, but also in combination with thrombolytic agents for the treatment of coronary thrombi. Recent data indicate a potential of abciximab alone to dissolve thrombi in vivo. We investigated the potential of abciximab, eptifibatide, and tirof...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200304000-00011

    authors: Moser M,Bertram U,Peter K,Bode C,Ruef J

    更新日期:2003-04-01 00:00:00

  • Felodipine analogs: structure-activity relationships.

    abstract::Several 3,5-pyridinedicarboxylic acid [4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-] esters, which are analogs to felodipine, were synthesized and tested for peroral activity and vascular selectivity. Structure-activity relationships demonstrate that felodipine has biological properties (selectivity and oral activ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198710001-00011

    authors: Berntsson P,Johansson E,Westerlund C

    更新日期:1987-01-01 00:00:00

  • Bioactivity of natriuretic peptide coinfusions; no evidence for unique effects of BNP in conscious sheep.

    abstract::Few studies have addressed the possibility that brain natriuretic peptide (BNP) possesses a profile of bioactivity that is distinct from that of atrial natriuretic peptide (ANP). Accordingly, we assessed the biologic actions of BNP in the setting of maximal or near-maximal ANP-induced biologic activity. Background ANP...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199902000-00008

    authors: Charles CJ,Espiner EA,Nicholls MG,Rademaker MT,Richards AM

    更新日期:1999-02-01 00:00:00

  • Human vascular smooth muscle cells have at least two distinct PDGF receptors and can secrete PDGF-AA.

    abstract::Platelet-derived growth factor (PDGF), a potent mitogen and chemoattractant for smooth muscle cells and fibroblasts in culture, is believed to play an important role in the formation of proliferative lesions of arterio-sclerosis. PDGF appears as three different dimeric isoforms: AA, AB, and BB. These were recently fou...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Hosang M,Rouge M

    更新日期:1989-01-01 00:00:00

  • Endothelin-1 and cardiotrophin-1 induce brain natriuretic peptide gene expression by distinct transcriptional mechanisms.

    abstract::Cardiotrophin-1 (CT-1) a novel IL-6-related cytokine, induces distinct hypertrophic responses to endothelin-1 (ET-1) on cultured neonatal rat cardiac myocytes. We found that ET-1 and CT-1 show a distinct pattern of gene induction of natriuretic peptides. Elucidation of the transcriptional mechanisms of brain natriuret...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199800001-00099

    authors: Kuwahara K,Saito Y,Ogawa Y,Tamura N,Ishikawa M,Harada M,Ogawa E,Miyamoto Y,Hamanaka I,Kamitani S,Kajiyama N,Takahashi N,Nakagawa O,Masuda I,Nakao K

    更新日期:1998-01-01 00:00:00

  • Central and peripheral alpha-adrenoceptor number and responsiveness after sinoaortic denervation in the rabbit.

    abstract::The effects of bilateral sinoaortic denervation were examined in rabbits in vivo and in vitro. In the in vivo studies the effects of intravenous administration of the alpha-adrenoceptor agonists phenylephrine and guanabenz and the antagonists prazosin and phentolamine on mean arterial pressure, heart rate, and plasma ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198207000-00007

    authors: Berthelot A,Hamilton CA,Petty MA,Reid JL

    更新日期:1982-07-01 00:00:00

  • Low-density lipoprotein inhibits receptor-mediated prostaglandin synthesis without affecting calcium and arachidonic acid mobilization in human endothelial cells.

    abstract::Vascular serotonin 5-HT1 receptors have quiescent constrictor activity that is activated by other vasoactive agents such as histamine. Previously, we observed that the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) potentiated histamine-stimulated arachidonic acid (AA) mobilization and prostaglandin production...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200411000-00015

    authors: Kilbourne EJ

    更新日期:2004-11-01 00:00:00

  • Cardiovascular response to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis.

    abstract::The cardiovascular response to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective putative 5-HT1A receptor agonist, has been investigated in the rat. Comparisons were made with clonidine, a centrally acting hypotensive agent with negligible affinity for 5-HT receptors. In conscious, spontaneously hyperte...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198703000-00010

    authors: Fozard JR,Mir AK,Middlemiss DN

    更新日期:1987-03-01 00:00:00

  • Is the ECG measure RSh a promising technique for detecting class I antiarrhythmic drug action in men?

    abstract::Previous animal experiments suggest that the increase in the amplitude from the R-wave to the S-wave (RSh) may be more sensitive than other ECG measures to sodium channel blocking drug actions. We measured RSh of three orthogonal leads at baseline and during intravenous pharmacologic stimulation with adenosine, ajmali...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00005344-199510000-00023

    authors: Wolzt M,Schmetterer L,Gouya G,Zanaschka G,Eichler HG

    更新日期:1995-10-01 00:00:00

  • Pioglitazone improves left ventricular diastolic function and decreases collagen accumulation in prediabetic stage of a type II diabetic rat.

    abstract::This study investigated the effect of pioglitazone, an insulin sensitizer, on metabolic abnormalities and oxidative stress as a cause of myocardial collagen accumulation in prediabetic rat hearts. Twenty male diabetic rats and 9 male nondiabetic age-matched rats were used. The diabetic rats were divided into two group...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200112000-00008

    authors: Tsuji T,Mizushige K,Noma T,Murakami K,Ohmori K,Miyatake A,Kohno M

    更新日期:2001-12-01 00:00:00

  • Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine(2A) antagonist, augments autologous bone marrow mononuclear cell implantation-induced improvement in endothelium-dependent vasodilation in patients with critical limb ischemia.

    abstract:BACKGROUND:The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT(2A) antagonist, on endothelial function in patients with critical limb ischemia (CLI). METHODS:We evaluated the leg blood flow (LBF) responses to ac...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/FJC.0b013e3181c37da4

    authors: Higashi Y,Miyazaki M,Goto C,Sanada H,Sueda T,Chayama K

    更新日期:2010-01-01 00:00:00

  • Antihypertensive efficacy of the combination of ketanserin + thiazide in hypertensives older than 50 years.

    abstract::The antihypertensive effect of the combination of ketanserin, a new antiserotonergic agent, and thiazide has been evaluated in 35 patients with arterial hypertension of mild to moderate degree in the greater than 50-year-old age group. Twenty patients were given ketanserin (20 mg) + hydrochlorothiazide (25 mg) (treatm...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Ferrara LA,Fasano ML,Soro S,Pasanisi F,Mancini M

    更新日期:1987-01-01 00:00:00

  • Long-term treatment of hypertension with methyldopa. I. Study objectives and design.

    abstract::In this retrospective study, a group of 435 patients provided meaningful analyses of blood pressure and dosage data for treatment periods of up to 4.5 years. The protocol, study objectives, and pretreatment demographic characteristics of the group are summarized in this report, which is the first in a series in this i...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章

    doi:

    authors: Itskovitz HD,Menduke H

    更新日期:1981-01-01 00:00:00

  • A phase I dose-escalation study to evaluate tolerability in a Western population to T89, a modern cardiovascular herbal medicine.

    abstract::T89 (Dantonic) is a modern herbal medicine currently used in Chinese hospitals for the management of ischemic heart disease. This dose-escalation clinical trial aims to assess tolerability of Western people to T89. Healthy Australian adults of non-Asian background orally took a single dosage of 6, 8, 10, 12, 13, 14, 1...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e31826f6179

    authors: Ling S,Luo RZ,Nheu L,Guo ZX,Sun H,Komesaroff PA

    更新日期:2012-12-01 00:00:00

  • Effect of rapamycin on rat aortic ring vasomotion.

    abstract::Rapamycin (RAPA) is an antifungal antibiotic with interesting new immunosuppressive properties. We evaluated RAPA's effects in vitro on basal and stimulated tension of isolated intact or denuded rat aortic rings. Rings were prepared in an organ chamber and contracted with 40 mM KCl (reference 100%). Some rings were tr...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199424050-00017

    authors: Corbin F,Blaise GA,Parent M,Chen H,Daloze PM

    更新日期:1994-11-01 00:00:00

  • Platelet activation by low-density lipoprotein and serotonin: effects of calcium antagonists.

    abstract::Epidemiological studies indicate that there are biological interrelationships between blood pressure and blood lipids that may influence the mechanisms whereby hypertension is associated with an increased risk of coronary artery disease. Serotonin (5-HT) and thromboxane A2, which are released from aggregating platelet...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Fetkovska N

    更新日期:1992-01-01 00:00:00

  • Ion channels, transporters, and pumps as targets for heart failure therapy.

    abstract::Congestive heart failure is a leading cause of morbidity and mortality. Congestive heart failure is marked by atrial and ventricular enlargements and reduced cardiac contractility and an association with an increased incidence of atrial and ventricular arrhythmias and sudden cardiac death. Dysfunctional ion channel fu...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/FJC.0b013e3181a1b9c7

    authors: Doshi D,Marx SO

    更新日期:2009-10-01 00:00:00

  • Amino acid 49 polymorphisms of the human beta1-adrenergic receptor affect agonist-promoted trafficking.

    abstract::The signaling impact of a human beta1-adrenergic receptor (beta1 AR) polymorphism at residue 49 of the aminoterminus (Ser-to-Gly substitution) was studied by recombinantly expressing each receptor. The two receptors displayed identical agonist and antagonist binding affinities. Furthermore, basal and agonist-stimulate...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200202000-00001

    authors: Rathz DA,Brown KM,Kramer LA,Liggett SB

    更新日期:2002-02-01 00:00:00

  • Effects of neutral endopeptidase inhibition on the clearance of exogenously administered endothelin in Sprague-Dawley rats.

    abstract::The effects of the selective neutral endopeptidase (EC 3.4.24.11, NEP) inhibitor SQ 28,603 on endogenous plasma endothelin (ET) concentration and on the clearance from the circulation of exogenously administered synthetic human ET-1 were examined in Sprague-Dawley rats. Inhibition of NEP by SQ 28,603 (100 mumol/kg int...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199304000-00018

    authors: Asaad MM,Dorso CR,Moreland SM

    更新日期:1993-04-01 00:00:00

  • Pharmacological characterization of PABSA, an orally active and highly potent endothelin-receptor antagonist.

    abstract::The pharmacological characterization of a nonpeptide endothelin (ET)-receptor antagonist, PABSA [(R)-(--)-2-(benzo[1,3]dioxol-5-yl)-N-(4-isopropyl-phenylsulfon yl)-2-(6-methyl-2-propylpyridin-3-yloxy)-acetamide hydrochloride] was studied. PABSA competitively inhibited the binding of [125I]-ET-1 to A7r5 cells expressin...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199907000-00022

    authors: Iwasaki T,Mihara S,Shimamura T,Kawakami M,Hayasaki-Kajiwara Y,Naya N,Fujimoto M,Nakajima M

    更新日期:1999-07-01 00:00:00

  • Impaired development of the thyroid and thymus in endothelin-1 knockout mice.

    abstract::We have previously demonstrated that endothelin-1 (ET-1) is essential to the development of neural crest-derived craniofacial and cardiovascular structures. In this study we evaluated the intrauterine growth and development of the thyroid and thymus glands in Edn1-/- homozygous mice. Edn1-/- homozygous mice were small...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:

    authors: Kurihara Y,Kurihara H,Maemura K,Kuwaki T,Kumada M,Yazaki Y

    更新日期:1995-01-01 00:00:00

  • Enhancement of ouabain arrhythmias by fatty acids.

    abstract::Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), whic...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198005000-00010

    authors: Sánchez-Serrano D,Alvarez JL,García-Barreto D

    更新日期:1980-01-01 00:00:00

  • Effects of p38 MAPK Inhibitor on angiotensin II-dependent hypertension, organ damage, and superoxide anion production.

    abstract::Angiotensin II (Ang II) activates p38 mitogen-activated protein kinase (p38 MAPK) and increases reactive oxygen species (ROS), but the nature of the relationship in vivo is not fully understood. We assess the effect of SB239063AN, a highly selective, orally active, p38 MAPK inhibitor, on Ang II-dependent hypertension,...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e318046f34a

    authors: Bao W,Behm DJ,Nerurkar SS,Ao Z,Bentley R,Mirabile RC,Johns DG,Woods TN,Doe CP,Coatney RW,Ohlstein JF,Douglas SA,Willette RN,Yue TL

    更新日期:2007-06-01 00:00:00

  • Electrophysiologic actions of d,l-sotalol and GLG-V-13 in ischemically injured canine epicardium.

    abstract::The electrophysiologic actions of the class III antiarrhythmic agents, GLG-V-13 and d,l-sotalol, were examined in superfused normal and ischemically injured epicardium. Both drugs produced concentration and reverse-use dependent prolongation of the action potential duration in normal myocardium without altering restin...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e3180ca959e

    authors: Patterson E,Scherlag BJ,Lazzara R,Garrison GL,Berlin KD

    更新日期:2007-09-01 00:00:00

  • Age-related changes in electromechanical properties of canine ventricular muscle: effect of ouabain.

    abstract::In this report, alterations between the electrical and mechanical responses of isolated neonatal and adult canine ventricular muscle preparations before and after ouabain exposure are described. No significant differences were observed between the two age groups in the concentration-dependent effects of ouabain on inc...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198911000-00002

    authors: Lathrop DA,Varró A,Gaum WE,Kaplan S

    更新日期:1989-11-01 00:00:00