Losartan and ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice.
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 microm in controls; p < 0.01) was eliminated by both ozagrel (61 +/- 2 microm) and losartan (63 +/- 2 microm).


CONCLUSIONS
Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II.
Department of Molecular and Cellular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Seungjun
S
Lee
Norman R
NR
Harris
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects*; D003251:Constriction, Pathologic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006943:Hyperglycemia / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008689:Methacrylates / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors; D014699:Venules / Q000473:pathology / Q000503:physiopathology
D047228:Angiotensin II Type 1 Receptor Blockers; D005343:Fibrinolytic Agents; D008689:Methacrylates; D013931:Thromboxanes; D000804:Angiotensin II; D019808:Losartan; C034364:ozagrel