Inducible nitric oxide synthase deficiency protects the heart from systolic overload-induced ventricular hypertrophy and congestive heart failure.

Abstract:

:Inducible nitric oxide synthase (iNOS) protein is expressed in cardiac myocytes of patients and experimental animals with congestive heart failure (CHF). Here we show that iNOS expression plays a role in pressure overload-induced myocardial chamber dilation and hypertrophy. In wild-type mice, chronic transverse aortic constriction (TAC) resulted in myocardial iNOS expression, cardiac hypertrophy, ventricular dilation and dysfunction, and fibrosis, whereas iNOS-deficient mice displayed much less hypertrophy, dilation, fibrosis, and dysfunction. Consistent with these findings, TAC resulted in marked increases of myocardial atrial natriuretic peptide 4-hydroxy-2-nonenal (a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) in wild-type mice but not in iNOS-deficient mice. In response to TAC, myocardial endothelial NO synthase and iNOS was expressed as both monomer and dimer in wild-type mice, and this was associated with increased reactive oxygen species production, suggesting that iNOS monomer was a source for the increased oxidative stress. Moreover, systolic overload-induced Akt, mammalian target of rapamycin, and ribosomal protein S6 activation was significantly attenuated in iNOS-deficient mice. Furthermore, selective iNOS inhibition with 1400W (6 mg/kg per hour) significantly attenuated TAC induced myocardial hypertrophy and pulmonary congestion. These data implicate iNOS in the maladaptative response to systolic overload and suggest that selective iNOS inhibition or attenuation of iNOS monomer content might be effective for treatment of systolic overload-induced cardiac dysfunction.

journal_name

Circ Res

journal_title

Circulation research

authors

Zhang P,Xu X,Hu X,van Deel ED,Zhu G,Chen Y

doi

10.1161/01.RES.0000264081.78659.45

subject

Has Abstract

pub_date

2007-04-13 00:00:00

pages

1089-98

issue

7

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000264081.78659.45

journal_volume

100

pub_type

杂志文章
  • Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats.

    abstract::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.6.1127

    authors: Anderson PG,Bishop SP,Digerness SB

    更新日期:1989-06-01 00:00:00

  • Morphometric evidence for non-pressure-related arterial wall thickening in hypertension.

    abstract::To investigate the relation of pressure and vascular wall thickening in hypertension, we coarcted the abdominal aorta upstream to the renal arteries in 14 rats. Sham-coarcted (n = 16) and two-kidney, one-clip (Goldblatt) hypertensive rats (n = 13) served as controls. Tail, femoral, and carotid arterial pressures rose ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.5.1001

    authors: Liu JL,Bishop SP,Overbeck HW

    更新日期:1988-05-01 00:00:00

  • Obesity and Cardiovascular Disease.

    abstract::The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.115.306883

    authors: Ortega FB,Lavie CJ,Blair SN

    更新日期:2016-05-27 00:00:00

  • RNA Splicing: Regulation and Dysregulation in the Heart.

    abstract::RNA splicing represents a post-transcriptional mechanism to generate multiple functional RNAs or proteins from a single transcript. The evolution of RNA splicing is a prime example of the Darwinian function follows form concept. A mutation that leads to a new mRNA (form) that encodes for a new functional protein (func...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.115.307872

    authors: van den Hoogenhof MM,Pinto YM,Creemers EE

    更新日期:2016-02-05 00:00:00

  • Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis.

    abstract::The remodeling of ventricular gap junctions, as defined by changes in size, distribution, or function, is a prominent feature of diseased myocardium. However, the regulation of assembly and maintenance of gap junctions remains poorly understood. To investigate N-cadherin function in the adult myocardium, we used a flo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000181132.11393.18

    authors: Li J,Patel VV,Kostetskii I,Xiong Y,Chu AF,Jacobson JT,Yu C,Morley GE,Molkentin JD,Radice GL

    更新日期:2005-09-02 00:00:00

  • minK-related peptide 1 associates with Kv4.2 and modulates its gating function: potential role as beta subunit of cardiac transient outward channel?

    abstract::Inherited mutations and a polymorphism in minK-related peptide 1 (MiRP1) have been linked to congenital or acquired long-QT syndrome, pointing to the importance of MiRP1 in maintaining the cardiac electrical stability. We tested whether MiRP1 could affect the function of Kv4.x (x=2 and 3), the major pore-forming (alph...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh1001.090839

    authors: Zhang M,Jiang M,Tseng GN

    更新日期:2001-05-25 00:00:00

  • Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response.

    abstract::Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and func...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000200162.94463.d7

    authors: Tzima E

    更新日期:2006-02-03 00:00:00

  • Decoding the cardiac message: the 2011 Thomas W. Smith Memorial Lecture.

    abstract::This review reflects and expands on the contents of my presentation at the Thomas W. Smith Memorial Lecture at American Heart Association Scientific Sessions, 2011. "Decoding the cardiac message" refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for,...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.111.256768

    authors: Dorn GW 2nd

    更新日期:2012-03-02 00:00:00

  • Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway.

    abstract::Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor tr...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/hh2001.097691

    authors: Silvestre JS,Bergaya S,Tamarat R,Duriez M,Boulanger CM,Levy BI

    更新日期:2001-10-12 00:00:00

  • The interferon stimulated gene 12 inactivates vasculoprotective functions of NR4A nuclear receptors.

    abstract:RATIONALE:Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. OBJECTIVE:The underlying mechanisms that regulate the activity of NR4A1 during vascula...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.111.258814

    authors: Papac-Milicevic N,Breuss JM,Zaujec J,Ryban L,Plyushch T,Wagner GA,Fenzl S,Dremsek P,Cabaravdic M,Steiner M,Glass CK,Binder CJ,Uhrin P,Binder BR

    更新日期:2012-04-13 00:00:00

  • Renovascular hypertension in mice with brain-selective overexpression of AT1a receptors is buffered by increased nitric oxide production in the periphery.

    abstract::We recently established a new transgenic mouse model with brain-restricted overexpression of angiotensin II (Ang II) type 1a receptors (NSE-AT(1a)) to unmask the role of the brain renin-angiotensin system in hypertension. To test the hypothesis that these mice would exhibit an early exacerbation of renovascular hypert...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000140892.86313.c2

    authors: Lazartigues E,Lawrence AJ,Lamb FS,Davisson RL

    更新日期:2004-09-03 00:00:00

  • Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange.

    abstract:RATIONALE:The sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317266

    authors: Rog-Zielinska EA,Scardigli M,Peyronnet R,Zgierski-Johnston CM,Greiner J,Madl J,O'Toole ET,Morphew M,Hoenger A,Sacconi L,Kohl P

    更新日期:2021-01-22 00:00:00

  • Attenuation of Myeloid-Specific TGFβ Signaling Induces Inflammatory Cerebrovascular Disease and Stroke.

    abstract:RATIONALE:Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence. OBJECTIVE:In this study, we investigated inflammation-associated stroke using a mouse model that ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.116.310349

    authors: Hollander MC,Latour LL,Yang D,Ishii H,Xiao Z,Min Y,Ray-Choudhury A,Munasinghe J,Merchant AS,Lin PC,Hallenbeck J,Boehm M,Yang L

    更新日期:2017-12-08 00:00:00

  • Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.

    abstract::Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), wh...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.45.2.267

    authors: Hopkins RA,Hammon JW Jr,McHale PA,Smith PK,Anderson RW

    更新日期:1979-08-01 00:00:00

  • Evidence for isoproterenol-induced phosphorylation of phosphatase inhibitor-1 in the intact heart.

    abstract::The positive inotropic effect of the beta-adrenoceptor agonist isoproterenol is accompanied by inhibition of phosphatase type 1 activity in myocardium. Indirect assays suggest that this effect is due to activation of protein phosphatase inhibitor-1, which inhibits phosphatase activity only when phosphorylated. To test...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.69.6.1450

    authors: Neumann J,Gupta RC,Schmitz W,Scholz H,Nairn AC,Watanabe AM

    更新日期:1991-12-01 00:00:00

  • Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.

    abstract::Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 ta...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000232324.87983.4b

    authors: Blankenberg S,Godefroy T,Poirier O,Rupprecht HJ,Barbaux S,Bickel C,Nicaud V,Schnabel R,Kee F,Morrison C,Evans A,Lackner KJ,Cambien F,Münzel T,Tiret L,AtheroGene Investigators.

    更新日期:2006-07-07 00:00:00

  • Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria.

    abstract::Although functional coupling between protein kinase Cepsilon (PKCepsilon) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCepsilon remain unknown. Based on recent evidence t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000069215.36389.8D

    authors: Baines CP,Song CX,Zheng YT,Wang GW,Zhang J,Wang OL,Guo Y,Bolli R,Cardwell EM,Ping P

    更新日期:2003-05-02 00:00:00

  • Block of sodium current by heptanol in voltage-clamped canine cardiac Purkinje cells.

    abstract::Heptanol blocks sodium current (INa) in nerve, but its effects on cardiac INa have not been well characterized. Block of INa by heptanol was studied in 16 internally perfused voltage-clamped cardiac Purkinje cells at reduced Na+ (45 mM outside, 0 mM inside). Heptanol block of peak sodium conductance was well described...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.4.977

    authors: Nelson WL,Makielski JC

    更新日期:1991-04-01 00:00:00

  • Suppression of angiotensin-converting enzyme expression and activity by shear stress.

    abstract::Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.80.3.312

    authors: Rieder MJ,Carmona R,Krieger JE,Pritchard KA Jr,Greene AS

    更新日期:1997-03-01 00:00:00

  • Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products.

    abstract::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000146030.53089.18

    authors: Yeh M,Cole AL,Choi J,Liu Y,Tulchinsky D,Qiao JH,Fishbein MC,Dooley AN,Hovnanian T,Mouilleseaux K,Vora DK,Yang WP,Gargalovic P,Kirchgessner T,Shyy JY,Berliner JA

    更新日期:2004-10-15 00:00:00

  • Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster.

    abstract::The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.6.1381

    authors: Capasso JM,Sonnenblick EH,Anversa P

    更新日期:1990-12-01 00:00:00

  • Heart failure gene therapy: the path to clinical practice.

    abstract::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.113.300269

    authors: Pleger ST,Brinks H,Ritterhoff J,Raake P,Koch WJ,Katus HA,Most P

    更新日期:2013-08-30 00:00:00

  • Intramural reentry as a mechanism of ventricular tachycardia during evolving canine myocardial infarction.

    abstract::We evaluated the contribution of intramural electrical events in initiation and maintenance of ventricular tachycardia in 15 dogs 3-8 days after either permanent (n = 2) or transient (n = 13) coronary artery occlusion. Seven of the dogs (47%) demonstrated eight distinct monomorphic ventricular tachycardia patterns whi...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.56.5.736

    authors: Kramer JB,Saffitz JE,Witkowski FX,Corr PB

    更新日期:1985-05-01 00:00:00

  • Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis.

    abstract::We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inact...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.3.525

    authors: Bennett MR,Evan GI,Newby AC

    更新日期:1994-03-01 00:00:00

  • Synergistic effects of acute hypoxemia and hypercapnic acidosis in conscious dogs. Renal dysfunction and activation of the renin-angiotensin system.

    abstract::The effects of acute hypoxemia and hypercapnic acidosis were examined in five unanesthetized dogs in which sodium intake was controlled at 80 mEq/24 hours for 4 days prior to study. Each animal was studied during combined acute hypoxemia and hypercapnic acidosis (Pao2 = 36 +/- 1 mm Hg, Paco2 = 52 +/- 1 mm Hg, pH = 7.1...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.53.2.202

    authors: Rose CE Jr,Kimmel DP,Godine RL Jr,Kaiser DL,Carey RM

    更新日期:1983-08-01 00:00:00

  • Pioglitazone-induced reductions in atherosclerosis occur via smooth muscle cell-specific interaction with PPAR{gamma}.

    abstract:RATIONALE:Peroxisome proliferator-activated receptor (PPAR)γ agonists attenuate atherosclerosis and abdominal aortic aneurysms (AAAs). PPARγ, a nuclear receptor, is expressed on many cell types including smooth muscle cells (SMCs). OBJECTIVE:To determine whether a PPARγ agonist reduces angiotensin II (Ang II)-induced ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.110.219089

    authors: Subramanian V,Golledge J,Ijaz T,Bruemmer D,Daugherty A

    更新日期:2010-10-15 00:00:00

  • Sodium-induced cardiac hypertrophy. Cardiac sympathetic activity versus volume load.

    abstract::To investigate the possible contributions of cardiac volume overload and cardiac sympathetic hyperactivity in the effects of sodium on cardiac mass, we evaluated the effects of treatment with saline (1%) and deoxycorticosterone acetate + saline (DOCA/saline) for 10 days and 3 and 6 weeks on ventricular anatomy and int...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.3.745

    authors: Fields NG,Yuan BX,Leenen FH

    更新日期:1991-03-01 00:00:00

  • Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model.

    abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000235869.50747.e1

    authors: Liu N,Colombi B,Memmi M,Zissimopoulos S,Rizzi N,Negri S,Imbriani M,Napolitano C,Lai FA,Priori SG

    更新日期:2006-08-04 00:00:00

  • Paradoxical dynamic interaction of heart period and vagal activity on atrioventricular conduction in the dog.

    abstract::The dynamic interaction of simultaneously changing heart period and single vagal stimuli on atrioventricular conduction (AV interval) was quantified by subtracting the vagally induced responses of the paced heart preparation from those of the unpaced heart preparation. This difference was significantly greater (P less...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.40.1.81

    authors: Martin P

    更新日期:1977-01-01 00:00:00

  • In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

    abstract:RATIONALE:During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.112.300806

    authors: Li RC,Tao J,Guo YB,Wu HD,Liu RF,Bai Y,Lv ZZ,Luo GZ,Li LL,Wang M,Yang HQ,Gao W,Han QD,Zhang YY,Wang XJ,Xu M,Wang SQ

    更新日期:2013-02-15 00:00:00