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Articles

Losartan and Ozagrel Reverse Retinal Arteriolar Constriction in Non-Obese Diabetic Mice

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Pages 379-387 | Received 11 Oct 2007, Accepted 26 Nov 2007, Published online: 10 Jul 2009
 

Abstract

Objective: Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II.

Methods: Using nonobese diabetic (NOD) mice, retinal measurements were performed three weeks following the age at which glucose levels exceeded 200 mg/dL, with accompanying experiments on age-matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities and were repeated following an injection of the thromboxane synthase inhibitor, ozagrel. Mice were subdivided into equal groups and given drinking water with or without the angiotensin II receptor antagonist, losartan.

Results: Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 ± 1 vs. 61 ± 1 μ m in controls; p < 0.01) was eliminated by both ozagrel (61 ± 2 μ m) and losartan (63 ± 2 μ m).

Conclusions: Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II.

ACKNOWLEDGMENT

The authors wish to thank Patsy Carter for helping with several technical aspects of the study.

This work was supported by the National Institutes of Health (EY017599; NRH).

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