<scp>l</scp>-Arginine restores endothelial nitric oxide synthase-coupled activity and attenuates monocrotaline-induced pulmonary artery hypertension in rats

Ou, Zhi‐Jun; Wei, Wei; Huang, Da-de; Luo, Wei; Luo, Dan; Wang, Zhiping; Zhang, Xi; Ou, Jing‐Song

doi:10.1152/ajpendo.00107.2010

Cited by 45 publications

(37 citation statements)

References 49 publications

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“…Reduction of NO bioactivity is a hallmark of endothelial dysfunction (1,12,29). Schumm et al (39) reported that endothelial function might be mediated by NO release in aortic stenosis.…”

Section: Discussionmentioning

confidence: 99%

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function

Chang

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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(HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O2˙Ϫ) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O2˙Ϫ generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease. endothelial microparticles; mitral valve; nitric oxide; endothelial nitric oxide synthase; heat shock protein 90

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“…Reduction of NO bioactivity is a hallmark of endothelial dysfunction (1,12,29). Schumm et al (39) reported that endothelial function might be mediated by NO release in aortic stenosis.…”

Section: Discussionmentioning

confidence: 99%

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function

Chang

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…2 An imbalance of vasoactive mediators has been known to play an important role in the progression of PAH. 3,4 In particular, reduced nitric oxide (NO) contributes to worsening of PAH. 5 NO is a vasoprotective molecule synthesized by endothelial NO synthase (eNOS), which is the predominant isoform of NOS.…”

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confidence: 99%

Cervical Ganglion Block Attenuates the Progression of Pulmonary Hypertension via Nitric Oxide and Arginase Pathways

Kim²,

Ryoo³

et al. 2014

Hypertension

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Abstract-It has been recognized that the sympathetic nervous system is activated in pulmonary arterial hypertension (PAH), and abnormal sympathetic hyperactivity leads to worsening of PAH via endothelial dysfunction. The purpose of this study was to examine whether sympathetic ganglion block (SGB) can treat PAH by increasing the availability of nitric oxide (NO). PAH was induced in rats by 50 mg/kg of subcutaneous monocrotaline. After 2 weeks, daily injections of ropivacaine into the left superior cervical ganglion were repeated for 14 days (monocrotaline-SGB group). Monocrotaline group received sham SGB with saline, whereas control group received saline instead of monocrotaline. PAH was evident in monocrotaline group, with right ventricular systolic pressures (47±4 mm Hg) that were higher than those of controls (17±2 mm Hg), whereas SGB significantly attenuated monocrotalineinduced PAH (35±4 mm Hg). The right/left ventricular mass ratios exhibited similar changes to those seen with right ventricular pressures. Heart rate variability showed significantly higher sympathetic activity in the monocrotaline group. Microscopy revealed a higher proportion of muscular arteries with thicker medial walls in the monocrotaline group, which was attenuated by SGB. Monocrotaline induced arginase hyperactivity, which was in turn decreased by SGB-induced endothelial NO synthase activation. SGB restored monocrotaline-induced hypoactivity of superoxide dismutase. In conclusion, SGB could suppress PAH and the remodeling of pulmonary arteries via inactivation of arginase and reciprocal elevation of NO bioavailability, thus attenuating disproportionate hyperactivation of the have been reported to attenuate the severity of symptoms and slow the progression of cardiovascular diseases including coronary artery disease, heart failure, and arrhythmias. According to the previous reports, there is a possibility that direct sympathetic nerve blocks are effective in patients with myocardial ischemia or systemic hypertension. 17,19 Given the relationship between sympathetic nervous system hyperactivity and endothelial dysfunction in patients with PAH, blockade of sympathetic hyperactivity may improve vascular reactivity by preserving endothelial function. To date, however, there is limited amount of data on the therapeutic effects of sympathetic ganglion block (SGB) on PAH. The purpose of the present study is to assess the therapeutic effects of SGB in a monocrotaline-induced PAH rat model. In parallel, we investigated whether SGB could attenuate the changes in arginase and NO bioavailability, as well as oxidative stress caused by monocrotaline. MethodsDetailed methods about animal preparation, experimental design, SGB, heart rate variability, hemodynamic analysis, right ventricular mass, pulmonary vessel morphometry, and NO (synthase)/arginase/ cGMP/oxidative stress assay are described in the online-only Data Supplement. Results Right Ventricular Systolic Pressure and Right Ventricular/Left Ventricular Mass RatioRight ventricular systolic pr...

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“…In mice, CR is evident to trigger NO [3,4], which is resulted from Akt-mediated eNOS up-regulation and activation [11]. ARG has been shown to enhance eNOS expression [26], but the effect of ART and SNP on eNOS has not been documented. According to the notion that NO non-covalently binds to COX and inhibits its activity [18], it should be reasonable that NO derived from the NO donor SNP or the NO precursor ARG can increase the AMP/ATP ratio and activate AMPK→Rac1→ Akt→eNOS signaling pathway [23].…”

Section: Discussionmentioning

confidence: 99%

Artemisinin mimics calorie restriction to initiate antioxidative responses and compromise telomere shortening

Wang

et al. 2014

Preprint

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Calorie restriction (CR) is known to extend lifespan among organisms with the putative mechanism underlying nitric oxide (NO)-enhanced mitochondrial biogenesis. However, whether NO maintains telomere intact that is implicated in life expectancy remains unknown. We report here the artemisinin derivative artesunate in a low concentration up-regulates mitochondrial SIRT3-SOD2 expression among global activation of antioxidative networks via the NO signaling cascade AMPK→Akt→ eNOS→SIRT1→PGC-1α. While the NO donor sodium nitroprusside and the NO precursor L-arginine replicate the antioxidative responses, exogenous low-dose hydrogen peroxide also leads to attenuated oxidative stress. The tumor suppressor BRCA1 and other DNA repair partners are down-regulated after scavenging of reactive oxygen species. Upon treatment, telomere shortening is damped without telomerase up-regulation, highlighting telomere maintenance rather than telomere elongation. In conclusion, artesunate can mimic CR to activate antioxidative responses and alleviate telomere attrition via NO signaling, thereby maintaining the stability and integrity of chromosomes, which are the hallmarks of longevity.

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l-Arginine restores endothelial nitric oxide synthase-coupled activity and attenuates monocrotaline-induced pulmonary artery hypertension in rats

Cited by 45 publications

References 49 publications

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function

Endothelial microparticles increase in mitral valve disease and impair mitral valve endothelial function

Cervical Ganglion Block Attenuates the Progression of Pulmonary Hypertension via Nitric Oxide and Arginase Pathways

Artemisinin mimics calorie restriction to initiate antioxidative responses and compromise telomere shortening

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