Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure

Dover, Anna R.; Chia, Stanley; Ferguson, James; Cruden, Nicholas L.; Megson, Ian L.; Fox, Keith A.A.; Newby, David E.

doi:10.1042/cs20060104

Cited by 11 publications

(7 citation statements)

References 47 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, our loss-of-function studies identify many genetic targets for NOS2 in GSCs (including the cell cycle inhibitor protein CDA1), providing novel mechanistic information distinct from previous studies using exogenous NO donors. Finally, NOS2 inhibition may represent an anti-glioma treatment option with an acceptably low toxicity profile, as demonstrated by the negligible toxicity of NOS2 inhibitor administration to humans (Brindicci et al, 2009; Dover et al, 2006; Singh et al, 2007). …”

Section: Discussionmentioning

confidence: 99%

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Eyler

Yan

et al. 2011

Cell

280

289

View full text Add to dashboard Cite

SUMMARY Malignant gliomas are aggressive brain tumors with limited therapeutic options, and improvements in treatment require a deeper molecular understanding of this disease. As in other cancers, recent studies have identified highly tumorigenic subpopulations within malignant gliomas, known generally as cancer stem cells. Here we demonstrate that glioma stem cells (GSCs) produce nitric oxide via elevated nitric oxide synthase-2 (NOS2) expression. GSCs depend on NOS2 activity for growth and tumorigenicity, distinguishing them from non-GSCs and normal neural progenitors. Gene expression profiling identified many NOS2-regulated genes, including the cell cycle inhibitor cell division autoantigen-1 (CDA1). Further, high NOS2 expression correlates with decreased survival in human glioma patients, and NOS2 inhibition slows glioma growth in a murine intracranial model. These data provide insight into how GSCs are mechanistically distinct from their less tumorigenic counterparts, and suggest that NOS2 inhibition may be an efficacious approach to treating this devastating disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Eyler

Yan

et al. 2011

Cell

280

289

View full text Add to dashboard Cite

show abstract

“…To our knowledge, the effects of 1400 W on foetal development are not known, even though this iNOS inhibitor has been used in a number or animal studies and in a few studies in humans [38, 39]. Moreover, while there is evidence supporting a pathogenic role for increased oxidative stress in clinical pre-eclampsia [8, 40], most clinical trials do not support antioxidant therapy for prevention or therapy of pre-eclampsia [41, 42].…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia

Amaral

Pinheiro

Guimaraes

et al. 2013

J Cellular Molecular Medi

View full text Add to dashboard Cite

Upregulation of inducible nitric oxide synthase (iNOS) has been reported in both experimental and clinical hypertension. However, although pro-inflammatory cytokines that up-regulate iNOS contribute to pre-eclampsia, no previous study has tested the hypothesis that a selective iNOS inhibitor (1400 W) could exert antihypertensive effects associated with decreased iNOS expression and nitrosative stress in pre-eclampsia. This study examined the effects of 1400 W in the reduced uteroplacental perfusion pressure (RUPP) placental ischaemia animal model and in normal pregnant rats. Sham-operated and RUPP rats were treated with daily vehicle or 1 mg/kg/day N-[3-(Aminomethyl) benzyl] acetamidine (1400 W) subcutaneously for 5 days. Plasma 8-isoprostane levels, aortic reactive oxygen species (ROS) levels and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were evaluated by ELISA, dihydroethidium fluorescence microscopy and lucigenin chemiluminescence respectively. Inducible nitric oxide synthase expression was assessed by western blotting analysis and aortic nitrotyrosine was evaluated by immunohistochemistry. Mean arterial blood pressure increased by ∼30 mmHg in RUPP rats, and 1400 W attenuated this increase by ∼50% (P < 0.05). While RUPP increased plasma 8-isoprostane levels, aortic ROS levels, and NADPH-dependent ROS production (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). Moreover, while RUPP increased iNOS expression and aortic nitrotyrosine levels (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). These results clearly implicate iNOS in the hypertension associated with RUPP. Our findings may suggest that iNOS inhibitors could be clinically useful in the therapy of pre-eclampsia, especially in particular groups of patients genetically more prone to express higher levels of iNOS. This issue deserves further confirmation.

show abstract

“…Moreover, elevated levels of ADMA have been proposed as a predictor of adverse cardiovascular outcomes in patients with heart failure [66]. In contrast, several clinical studies have demonstrated that patients with heart failure exhibit an increased responsiveness to inhibitors of NO synthesis and elevated plasma levels of stable NO breakdown products [67-70], suggesting that NO synthesis is increased rather than decreased. …”

Section: L-arginine – No Pathway In Chronic Heart Failurementioning

confidence: 99%

The Role of Exercise on L-Arginine Nitric Oxide Pathway in Chronic Heart Failure

Mendes-Ribeiro¹,

Mann

Meirelles³

et al. 2009

Open Biochem J

View full text Add to dashboard Cite

Chronic heart failure (CHF) is a pathological state with high morbidity and mortality and the full understanding of its genesis remain to be elucidated. In this syndrome, a cascade of neurohormonal and hemodynamic mechanisms, as well as inflammatory mediators, are activated to improve the impaired cardiac function. Clinical and experimental observations have shown that CHF is associated with a generalized disturbance in endothelium-dependent vasodilation, which may contribute to the progression of ventricular and vascular remodelling in this syndrome. There is also accumulating evidence that disturbances in nitric oxide (NO) availability is involved in the development of heart failure at the systemic and cardiac levels. NO is a ubiquitous signalling molecule which causes potent vasodilation, inhibits platelet activation and regulates the contractile properties of cardiac myocytes. It is generated from the amino acid L-arginine via constitutive and inducible isoforms of the enzyme NO synthase (NOS). There is evidence that exercise, a nonpharmacological tool, improves symptoms, fitness (VO2peak), quality of life and NO bioavailability in CHF population. This review examines different aspects of the L-arginine-NO pathway and inflammation in the physiopathology of CHF and highlights the important beneficial effects of exercise in this disease.

show abstract

Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure

Cited by 11 publications

References 47 publications

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Glioma Stem Cell Proliferation and Tumor Growth Are Promoted by Nitric Oxide Synthase-2

Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre‐eclampsia

The Role of Exercise on L-Arginine Nitric Oxide Pathway in Chronic Heart Failure

Contact Info

Product

Resources

About