Differential effects of diet-induced dyslipidemia and hyperglycemia on mesenteric resistance artery structure and function in type 2 diabetes

Kamakshi Sachidanandam, Jim R. Hutchinson, Mostafa M. Elgebaly, Erin M. Mezzetti, Mong Heng Wang, Adviye Ergul

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19 Scopus citations

Abstract

Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and matrix me- talloproteinase dynamics], mechanical properties (vessel stiffness), and reactivity to pressure and vasoactive factors were measured in third-order mesenteric arteries in control Wistar and type 2 diabetic Goto-Kakizaki (GK) rats fed either a regular or high-fat diet. M/L ratios, total collagen, and myogenic tone were increased in diabetes. Addition of the high-fat diet altered collagen patterns (mature versus new collagen) in favor of matrix accumulation. Addition of a high-fat diet caused increased constriction to endothelin-1 (0.1-100 nM), showed impaired vasorelaxation to both acetylcholine (0.1 nM-1 μM) and sodium nitroprusside (0.1 nM-1 μM), and increased cardiovascular risk factors in diabetes. These results suggest that moderate elevations in blood glucose, as seen in our lean GK model of type 2 diabetes, promote resistance artery remodeling resulting in increased medial thickness, whereas addition of a high-fat diet contributes to diabetic vascular disease predominantly by impairing vascular reactivity in the time frame used for this study. Although differential in their vascular effects, both hyperglycemia and diet-induced dyslipidemia need to be targeted for effective prevention and treatment of diabetic vascular disease.

Original languageEnglish (US)
Pages (from-to)123-130
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume328
Issue number1
DOIs
StatePublished - Jan 1 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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