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

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 metalloproteinase 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 microM) and sodium nitroprusside (0.1 nM-1 microM), 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.

• Authors: Kamakshi Sachidanandam, Jim R Hutchinson, Mostafa M Elgebaly, Erin M Mezzetti, Mong-Heng Wang, Adviye Ergul
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 328 Issue 1 Pg. 123-30 (Jan 2009) ISSN: 1521-0103 [Electronic] United States
• PMID: 18941121 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Nitroprusside
• Collagen
• Matrix Metalloproteinases
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Angiography
• Animals
• Collagen (metabolism)
• Diabetes Mellitus, Type 2 (epidemiology, physiopathology)
• Diabetic Angiopathies (chemically induced, physiopathology, prevention & control)
• Dietary Fats (adverse effects)
• Disease Models, Animal
• Dyslipidemias (complications, physiopathology)
• Humans
• Hyperglycemia (complications, physiopathology)
• Male
• Matrix Metalloproteinases (metabolism)
• Mesenteric Arteries (physiology, physiopathology)
• Nitroprusside (pharmacology)
• Rats
• Rats, Wistar
• Risk Factors
• Vascular Resistance (physiology)
• Vasoconstriction
• Vasodilation (drug effects)