Attenuation of Hypertension Development by Aminoguanidine in Spontaneously Hypertensive Rats: Role of Methylglyoxal
Methylglyoxal (MG), a metabolite of glucose, and MG-induced advanced glycation endproducts (AGEs) are causatively associated with vascular complications of diabetes mellitus. We have previously reported elevated levels of MG and MG-induced AGEs in spontaneously hypertensive rats (SHR). The purpose o...
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Published in | American journal of hypertension Vol. 20; no. 6; pp. 629 - 636 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Inc
01.06.2007
Oxford University Press Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | Methylglyoxal (MG), a metabolite of glucose, and MG-induced advanced glycation endproducts (AGEs) are causatively associated with vascular complications of diabetes mellitus. We have previously reported elevated levels of MG and MG-induced AGEs in spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the causative role of MG and MG-induced AGEs in the pathogenesis of hypertension in SHR.
Young SHR were treated with an AGE inhibitor, aminoguanidine, for 9 weeks. HPLC was used to determine plasma and aortic MG and reduced glutathione levels. The MG-induced AGEs,
Nε-carboxyethyl-lysine (CEL) and argpyramidine, in the aorta were determined by immunohistochemistry. Vascular relaxation of small mesenteric arteries was measured using myograph.
Chronic treatment with aminoguanidine attenuated age-dependent blood pressure (BP) increase in SHR. Plasma and aortic MG levels, and aortic levels of MG-induced AGEs, were significantly reduced after aminoguanidine treatment, which were comparable to those from age-matched Wistar Kyoto rats. Free radical level was significantly lowered, whereas reduced glutathione level was significantly increased by aminoguanidine treatment in the aortic tissues from SHR. Moreover, aminoguanidine therapy prevented the morphologic damage of vascular tissues in SHR and restored the endothelium-dependent relaxation to acetylcholine. Chronic aminoguanidine treatment also increased aortic endothelial nitric oxide synthase expression and reduced inducible nitric oxide synthase expression.
The MG and MG-induced AGEs contribute to the pathogenesis of hypertension by altering the redox balance, causing vascular eutrophic inward remodeling, and inducing endothelial dysfunction in SHR. |
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Bibliography: | ark:/67375/HXZ-9DQ0TG8B-G href:20_6_629.pdf istex:398B7C09D7045F96CCEE3531BA43ACECCCAB5D8B This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR, MOP-68938) and the Heart and Stroke Foundation of Canada to L. Wu. L. Wu is supported by a New Investigator Award from CIHR. X. Wang is supported by a Doctoral Research Award from CIHR/Canadian Hypertension Society. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0895-7061 1879-1905 1941-7225 |
DOI: | 10.1016/j.amjhyper.2006.12.003 |