Mechanisms Mediating the Protective Effect of Curcumin on Vascular Endothelial Dysfunction Induced by High Glucose
Journal Title: Journal of Physiology and Pharmacology Advances - Year 2013, Vol 3, Issue 3
Abstract
To investigate the antioxidant and vascular protective effect of curcumin, principle curcuminoid (a natural phenol) of the popular Indian spice and traditional medicine turmeric, on vascular endothelial dysfunction subsequent to high glucose stress. Thoracic aortic rings, obtained from male wistar rats were mounted in an organ bath and isometric contraction recorded. Rings were preconstricted with phenylephrine (PE, 10-5M), endothelium dependent relaxation was observed by using acetylcholine (ACh) and endothelium independent relaxation was observed by using sodium nitroprusside (SNP). Proto porphorin IX zinc (ZnPPIX), a specific heme oxygenase-1 (HO-1) inhibitor, was used to evaluate the possible role of HO-1 enzyme. Methylene blue (MB), a non-specific guanylate cyclase (GC) inhibitor, was used to understand the possible role of GC enzyme in this protective action. After incubation with 44mmol/L of high glucose for 2hrs, the vascular relaxation responses to acetylcholine (Ach) (10-8 to 10-5mol/L) were significantly decreased (Ach max. response NG: 85±3% versus HG: 64±2.7%, p<0.001, Student’s t test) in vascular rings. Co-incubation with curcumin (CUR) (10-11mol/L) and high glucose reversed the high glucose induced vasodilation dysfunction (Ach max. response HG: 64±2.7%, p<0.001 versus HG+CUR: 82±1%, Student’s t test). Protoporphyrin IX Zinc (ZnPPIX) (10- 6mol/L) an inhibitor of HO-1 offset the protective effects of curcumin. Furthermore, GC inhibition with methylene blue (MB) (10-6mol/L) completely abolished the protective effects of curcumin. Curcumin could alleviate the high glucose induced acute endothelium dependant vascular dysfunction in rat thoracic aortic rings. Increased HO-1 activity and stimulation of GC may be proposed as a mechanism to account for this protective action of curcumin.
Authors and Affiliations
R. K. C. Mangipudi , C. Hillier , P. Chintareddy , S. Tsuro
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