Attenuation of acetylcholine mediated coronary vasoconstriction with nonvasodilating dose of nitroglycerin in patients with heart failure: evidence for nitroglycerin induced enhancement of endogenous nitric oxide effect?

The heart is one of the organs most vulnerable to sepsis. This review describes the general characteristics of sepsis-induced cardiomyopathy and the main pathogenesis of myocardial dysfunction in sepsis. Levosimendan is a novel drug for treatment of sepsis-induced myocardial dysfunction. This review also elaborates on the pathogenesis of levosimendan, including the mechanisms of its anti-inflammatory effects, improvement of myocardial ischaemia, increased synthesis of nitric oxide, vascular endothelial cell protection, increased myocardial contractility, improved diastolic function, and inhibition of hypoxia-inducible factor-1α expression. Many clinical studies have proven that levosimendan effectively prevents myocardial dysfunction in sepsis. In addition to the widespread use of levosimendan in patients with heart failure, the role of levosimendan in the treatment of patients with sepsis-induced cardiomyopathy will be increasingly studied and applied in the future.

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Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular Diseases

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/619207 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Xiaoyu Liu ◽

John Fassett ◽

Yidong Wei ◽

Yingjie Chen

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Congestive Heart Failure ◽

Cardiovascular Diseases ◽

Therapeutic Target ◽

Farnesoid X Receptor ◽

Nitric Oxide Synthase Inhibitor ◽

Endogenous Nitric Oxide ◽

Synthase Inhibitor ◽

Nitric Oxide Bioavailability

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor that blocks nitric oxide production, while congestive heart failure is associated with increased plasma and tissue ADMA content. Increased plasma ADMA is a strong and independent predictor of all-cause mortality in the community and the strongest predictor of mortality in patients after myocardial infarction. Recent studies demonstrated that dimethylarginine dimethylaminohydrolase-1 (DDAH1) is the critical enzyme for ADMA degradation and thereby plays an important role in maintaining cardiovascular nitric oxide bioavailability. Interestingly, activation of the farnesoid X receptor (FXR) through the bile acid ursodeoxycholic acid (UDCA) or synthetic FXR agonists, such as GW4064, can increase DDAH1 expression. Thus, modulating DDAH1 activity through FXR receptor agonists such as UDCA could be a therapeutic target for treating reduced nitric oxide bioavailability in congestive heart failure and other cardiovascular diseases.

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Endogenous Nitric Oxide Modulates Human Cardiac Vagal Activity in Heart Failure

Clinical Science ◽

10.1042/cs100020pb ◽

2001 ◽

Vol 100 (s44) ◽

pp. 20P-20P

Author(s):

S Chowdhary ◽

JH Coote ◽

JN Townend

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Vagal Activity ◽

Endogenous Nitric Oxide

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Increased l-arginine Transport in Human Erythrocytes in Chronic Heart Failure

Clinical Science ◽

10.1042/cs0940043 ◽

1998 ◽

Vol 94 (1) ◽

pp. 43-48 ◽

Cited By ~ 20

Author(s):

H. Hanssen ◽

T. M. C. Brunini ◽

M. Conway ◽

A. P. Banning ◽

N. B. Roberts ◽

...

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Chronic Heart Failure ◽

Human Erythrocytes ◽

Transport Systems ◽

Acid Transport ◽

Cationic Amino Acid ◽

Arginine Transport ◽

Healthy Donors ◽

Patients With Heart Failure

1. Transport of l-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of l-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L. 3. The Vmax for l-arginine transport via system y+ increased from 292 to 490 μmol h−-1 l−-1 of cells in heart failure. 4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of l-arginine via system y+L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of l-arginine and l-leucine influx by NG-monomethyl-l-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma l-arginine levels were reduced in patients with heart failure (59 μmol/l) compared with controls (125 μmol/l). Plasma from patients with heart failure also contained the endogenous l-arginine analogue NG-monomethyl-l-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of l-arginine and NG-monomethyl-l-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for l-arginine and NG-monomethyl-l-arginine. 8. The present study provides the first evidence that system y+ mediates the increased transport of l-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of l-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the l-arginine-nitric oxide signalling pathway.

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Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00473.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. H2332-H2341 ◽

Cited By ~ 80

Author(s):

Hong Zheng ◽

Yi-Fan Li ◽

Kurt G. Cornish ◽

Irving H. Zucker ◽

Kaushik P. Patel

Keyword(s):

Nitric Oxide ◽

Heart Failure ◽

Exercise Training ◽

Paraventricular Nucleus ◽

No Donor ◽

Protein Levels ◽

Arterial Blood ◽

Endogenous Nitric Oxide ◽

Dose Dependent

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 ± 17 vs. 99 ± 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, NG-monomethyl-l-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.

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