Attenuation of Hypertension Development by Aminoguanidine in Spontaneously Hypertensive Rats: Role of Methylglyoxal

• Published in: American journal of hypertension Vol. 20; no. 6; pp. 629 - 636
• Main Authors: Wang, Xiaoxia, Chang, Tuanjie, Jiang, Bo, Desai, Kaushik, Wu, Lingyun
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2007; Oxford University Press; Elsevier Science
• Subjects: advanced glycation end products; Animals; Aorta - metabolism; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - therapeutic use; Experimental diseases; Free Radicals - metabolism; Glutathione - metabolism; Glycation End Products, Advanced - metabolism; Guanidines - therapeutic use; hypertension; Hypertension - metabolism; Hypertension - prevention & control; Male; Medical sciences; Mesenteric Arteries - drug effects; Mesenteric Arteries - pathology; Methylglyoxal; Nitric Oxide Synthase - metabolism; Oxidation-Reduction; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pyruvaldehyde - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Methylglyoxal; advanced glycation end products; hypertension; Hypertension; Vertebrata; Mammalia; Rat; Animal; Rodentia; Cardiovascular disease
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2006.12.003

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.