Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells

Chicoine, Louis G.; Paffett, Michael L.; Young, Tamara L.; Nelin, Leif D.

doi:10.1152/ajplung.00194.2003

Cited by 139 publications

(208 citation statements)

References 27 publications

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“…Consistent with this hypothesis, increased vascular arginase activity was reported to contribute to decreased endotheliumdependent NO production in pathologic conditions such as hypertension (19,20), atherosclerosis (21), diabetes (22), and erectile dysfunction (23), or in aging (24). Moreover, even though the regulating factors of arginase expression/activity remain largely unknown, it was demonstrated that various proinflammatory cytokines can act as inducers of arginase expression in cultured endothelial cells (18,25,26).…”

mentioning

confidence: 78%

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Prati¹,

Berthelot²,

Wendling³

et al. 2011

Arthritis & Rheumatism

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Objective. To investigate whether arginase pathway abnormalities occur in vessels from rats with adjuvant-induced arthritis (AIA), and to determine whether the up-regulation of arginase, which reciprocally regulates nitric oxide synthase (NOS) by competing for the same substrate, L-arginine, contributes to endothelial dysfunction in AIA.Methods. We performed vascular reactivity experiments on thoracic aortic rings from AIA rats and control rats, and we investigated the response of rings to norepinephrine (NE), sodium nitroprusside (SNP), and acetylcholine (ACh). ACh-induced relaxation was evaluated in the presence (or not in the presence) of the NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME), the arginase inhibitor N -hydroxy-nor-Larginine (nor-NOHA), or both. Aortic arginase activity was measured using a spectrophotometric method, and the expression of arginase and endothelial NOS (eNOS) was evaluated by Western blotting.Results. ACh-induced vasodilation was significantly impaired in AIA rats, while the responses to NE and to SNP did not differ from those in control rats. L-NAME reduced ACh-induced vasodilation to a lesser extent in AIA rats than in control rats. Incubation of aortic rings with nor-NOHA enhanced the vascular response to ACh in AIA rats and reversed the effects of L-NAME. Compared with control rats, AIA rats exhibited increased vascular expression of arginase II (by 22%) (P < 0.05) as well as increased arginase activity (by 49%) (P < 0.05), whereas eNOS expression was unchanged. Finally, arginase activity and expression correlated positively with arthritis severity.Conclusion. Our results are consistent with the notion that arginase up-regulation plays a role in AIAassociated endothelial dysfunction. They suggest that arginase might be an attractive new target for treating endothelial dysfunction in arthritis.

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mentioning

confidence: 78%

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Prati¹,

Berthelot²,

Wendling³

et al. 2011

Arthritis & Rheumatism

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“…Arginase I expression in macrophages, hepatocytes, and vascular smooth muscle cells, is stimulated by lipopolysaccharide (LPS), tumor necrosis factor-α, IL-13, altered oxygen tension, and balloon dilatation of coronary arteries [7][8][9][10][11]. The activation and expression of endothelial arginase II can also be induced by a variety of vascular stimulants, including OxLDL, LPS, TNF-α, IFN-γ, 8-bromocGMP, and hypoxia [7,10,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Arginase Inhibition by Ethylacetate Extract ofCaesalpinia sappanLignum Contributes to Activation of Endothelial Nitric Oxide Synthase

Shin

Cuong

Lee

et al. 2011

Korean J Physiol Pharmacol

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“…Previously, Berkowitz et al (6) had shown that both arginase isotypes were expressed in the rat aortic endothelium. Arginase I had been found to be constitutively expressed in endothelial cells (35), whereas arginase II appeared to be inducible in response to cytokines (8). White et al (32) have demonstrated that arginase type I knockdown could enhance NOS activity in adult rat thoracic aortic tissue, and Zhang et al (35) had shown in the porcine coronary artery that arginase type I is responsible for modulating the endothelial-dependent relaxation.…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in arginase expression and activity in the lung

Belik

Shehnaz²,

Pan³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Arginases compete with nitric oxide (NO) synthases for L-arginine as common substrate. Pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation. The developmental patterns of arginase activity and type I and II isoforms expression in the lung have not been previously evaluated. Hypothesizing that lung arginase activity is developmentally regulated and highest in the fetus, we measured the expression of both arginase isoforms and total arginase activity in fetal, newborn, and adult rat lung, pulmonary artery, and bronchial tissue. In addition, intrapulmonary arterial muscle force generation was evaluated in the absence and presence of the arginase inhibitor N -hydroxy-nor-L-arginine (nor-NOHA). Arginase II content, as well as total arginase activity, was highest in fetal rat lung, bronchi, and pulmonary arterial tissue and decreased with age (P Ͻ 0.05), and its lung cell expression was developmentally regulated. In the presence of nor-NOHA, pulmonary arterial force generation was significantly reduced in fetus and newborn (P Ͻ 0.01). No significant change in force generation was noted in bronchial tissue following arginase inhibition. In conclusion, arginase II is regulated developmentally, and both expression and activity are maximal during fetal life. We speculate that the maintenance of a high pulmonary vascular resistance and decreased lung NO production prenatally may, in part, be dependent on increased arginase expression and/or activity. pulmonary vascular resistance; airway resistance; nitric oxide GIVEN THE HIGH FETAL PULMONARY vascular resistance, pulmonary blood flow prenatally is less than 10% of the total cardiac output. Pulmonary vascular resistance rapidly decreases at birth and reaches the low physiological level of adults at the end of the neonatal period (12). The factors accounting for maintenance of high pulmonary vascular resistance prenatally and its rapid decrease after birth are not completely understood. Pulmonary vascular nitric oxide (NO) availability and its relaxant effect on smooth muscle are considered to play an important role in the transition from fetal to neonatal circulation (1).NO is produced by nitric oxide synthases (NOS). In the lung, three NOS isoforms are present. Endothelial NOS (eNOS) is expressed in pulmonary vascular endothelium and bronchial epithelium, whereas neuronal (nNOS) and inducible (iNOS)

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Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells

Cited by 139 publications

References 27 publications

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Arginase Inhibition by Ethylacetate Extract ofCaesalpinia sappanLignum Contributes to Activation of Endothelial Nitric Oxide Synthase

Developmental changes in arginase expression and activity in the lung

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