Abstract
The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / blood
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Angiotensin II / genetics
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Animals
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Aorta, Thoracic / drug effects*
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Aorta, Thoracic / metabolism
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Aorta, Thoracic / pathology
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Blood Pressure / drug effects
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Cells, Cultured
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Dietary Carbohydrates / adverse effects*
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Fructose / adverse effects*
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Gene Expression Regulation / drug effects*
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Glutathione / blood
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Kidney / drug effects*
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Kidney / metabolism
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Kidney / pathology
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Male
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Muscle, Smooth, Vascular / pathology
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Myocytes, Smooth Muscle / drug effects
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Myocytes, Smooth Muscle / metabolism
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Myocytes, Smooth Muscle / pathology
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NF-kappa B / blood
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NF-kappa B / genetics
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Pyruvaldehyde / blood*
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Pyruvaldehyde / pharmacology
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RNA, Messenger / blood
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Receptor for Advanced Glycation End Products
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Receptor, Angiotensin, Type 1 / blood
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Receptor, Angiotensin, Type 1 / genetics
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Receptors, Adrenergic, alpha-1 / blood
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Receptors, Adrenergic, alpha-1 / genetics
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Receptors, Immunologic / blood
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Receptors, Immunologic / genetics
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Renin / blood
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Renin / genetics
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Renin-Angiotensin System / drug effects*
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Renin-Angiotensin System / genetics
Substances
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Dietary Carbohydrates
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NF-kappa B
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RNA, Messenger
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Receptor for Advanced Glycation End Products
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Receptor, Angiotensin, Type 1
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Receptors, Adrenergic, alpha-1
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Receptors, Immunologic
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Angiotensin II
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Fructose
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Pyruvaldehyde
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Renin
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Glutathione
Grants and funding
This work was supported by a grant-in-aid from the Heart and Stroke Foundation of Saskatchewan (G-10-DE-4379) to KD and LW, and by a New Investigator grant from the Saskatchewan Health Research Foundation to KD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.