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hypoxia, ADMA, DDAH

Nikki Buijs, J Efraim Oosterink, Morgan Jessup, Henk Schierbeek, Donna B Stolz, Alexander P Houdijk, David A Geller, Paul A van Leeuwen
BACKGROUND: Anti-angiogenic therapies, targeting VEGF, are a promising treatment for hepatocellular carcinoma (HCC). To enhance this potential therapy, identification of novel targets in this pathway is of major interest. Nitric oxide (NO) plays a crucial role in VEGF-dependent angiogenesis. NO production depends on arginine as substrate and asymmetric dimethylarginine (ADMA) as inhibitor. Dimethylarginine dimethylaminohydrolase 1 (DDAH-1) catabolizes ADMA and therefore regulates NO and VEGF expression...
November 2017: Angiogenesis
Nicole Lüneburg, Patricia Siques, Julio Brito, Karem Arriaza, Eduardo Pena, Hans Klose, Fabiola Leon-Velarde, Rainer H Böger
Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days...
2016: Pulmonary Medicine
Shiro Mizuno, Takeshi Ishizaki, Hirohisa Toga, Akio Sakai, Jainagul Isakova, Elnura Taalaibekova, Zamirbek Baiserkeev, Baktybek Kojonazarov, Almaz Aldashev
Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks...
2015: BioMed Research International
Nicole Lüneburg, Lars Harbaum, Jan K Hennigs
Since its discovery, many adhere to the view that asymmetric dimethylarginine (ADMA), as an inhibitor of the synthesis of nitric oxide (NO), contributes to the pathogenesis of various diseases. Particularly, this is evident in disease of the cardiovascular system, in which endothelial dysfunction results in an imbalance between vasoconstriction and vasodilatation. Even if increased ADMA concentrations are closely related to an endothelial dysfunction, several studies pointed to a potential beneficial effect of ADMA, mainly in the context of angioproliferative disease such as cancer and fibrosis...
2014: BioMed Research International
Ya-Ning Zhou, Ming-Yu Sun, Yong-Ping Mu, Tao Yang, Bing-Bing Ning, Shuang Ren, Jia-Mei Chen, Ping Liu
ETHNOPHARMACOLOGICAL RELEVANCE: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. MATERIAL AND METHODS: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl₄) in C57BL/6 mice for 6 weeks...
May 14, 2014: Journal of Ethnopharmacology
Seldag Bekpinar, Seval Develi-Is, Yesim Unlucerci, Zeynep Kusku-Kiraz, Mujdat Uysal, Figen Gurdol
Plasma levels of asymmetric dimethylarginine (ADMA) are known to be elevated under pathological conditions, but reports on intracellular ADMA levels are scarce. In this study, we investigated whether lipopolysaccharide (LPS)-induced endotoxemia alters the intra- and extra-cellular partition of l-arginine and ADMA. The effect of H2S pretreatment was also researched. Wistar rats were given sodium hydrogen sulfide (NaHS, 1 mg·(kg body mass)(-1)) one hour before the LPS injections (20 mg·kg(-1)). Six hours after the LPS treatment, the animals were sacrificed...
December 2013: Canadian Journal of Physiology and Pharmacology
Jessica Kr Boult, Simon Walker-Samuel, Yann Jamin, James M Leiper, Guy St J Whitley, Simon P Robinson
Dimethylarginine dimethylaminohydrolase (DDAH) metabolizes the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine (ADMA). Constitutive over-expression of DDAH1, the isoform primarily associated with neuronal nitric oxide synthase (nNOS) results in increased tumour growth and vascularization, and elevated VEGF secretion. To address whether DDAH1-mediated tumour growth is reliant upon the enzymatic activity of DDAH1, cell lines expressing an active site mutant of DDAH1 incapable of metabolizing ADMA were created...
November 2011: Journal of Pathology
Ryo Shibata, Seiji Ueda, Sho-Ichi Yamagishi, Yusuke Kaida, Yuriko Matsumoto, Kei Fukami, Ayako Hayashida, Hidehiro Matsuoka, Seiya Kato, Masumi Kimoto, Seiya Okuda
BACKGROUND: Decreased peritubular capillary (PTC) flow due to impaired endothelial function elicits tubulointerstitial ischaemia, thereby enhancing renal damage in chronic kidney disease, including diabetic nephropathy. Since nitric oxide (NO) is a vasodilator and known to play an important role in the maintenance of PTC flow, it is conceivable that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may cause tubulointerstitial ischaemia, thus being involved in the progression of diabetic nephropathy...
April 2009: Nephrology, Dialysis, Transplantation
Lesley J Millatt, Guy StJ Whitley, Dechun Li, James M Leiper, Helmy M Siragy, Robert M Carey, Roger A Johns
BACKGROUND: Chronic hypoxia-induced pulmonary hypertension is associated with increased pulmonary expression of nitric oxide synthase (NOS) enzymes. Nevertheless, some reports have indicated decreased pulmonary production of NO in the disease. To address this paradox, we determined pulmonary concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) in the hypoxia-induced pulmonary hypertension rat model. In addition, we determined whether dysregulation of the ADMA-metabolizing enzyme dimethylarginine dimethylaminohydrolase I (DDAH I) plays a role in this disease...
September 23, 2003: Circulation
Francesca I Arrigoni, Patrick Vallance, Sheila G Haworth, James M Leiper
BACKGROUND: Nitric oxide (NO) plays an important part in lowering pulmonary vascular resistance after birth, and in persistent pulmonary hypertension of the newborn (PPHN), NO-mediated dilation is dysfunctional. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) circulates in plasma, and its concentrations are elevated in certain cardiovascular diseases, including pulmonary hypertension. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the activity of which regulates ADMA concentrations and provides a mechanism for modulating NO synthase in vivo...
March 4, 2003: Circulation
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