Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat.
Arterial hypertension has been identified as a major secondary risk factor for diabetic retinopathy. However, the mechanisms by which hypertension worsens retinopathy are unknown. Inhibition of advanced glycation product formation prevents the development of experimental diabetic retinopathy in normotensive diabetic rats. In this study the effect of hypertension on the rate of diabetic retinopathy development and the formation of arteriolar thrombosis was evaluated. We also evaluated the effect of aminoguanidine, an inhibitor of advanced glycation and product formation on retinal pathology of diabetic hypertensive rats. After 26 weeks of diabetes, hypertension accelerated the development of retinopathy despite a lower mean blood glucose level than in the non-hypertensive group (diabetic spontaneous hypertensive rats (SHR) 16.00 +/- 6.83 mmol/l; diabetic normotensive Wistar Kyoto rats (WKY) 34.9 +/- 3.64 mmol/l; p < 0.0001). Diabetic SHR had nearly twice as many acellular capillaries as diabetic WKY (SHR diabetic: 91.9 +/- 7.5 acellular capillaries per mm2 of retinal area vs WKY diabetic: 53.7 +/- 8.5 acellular capillaries per mm2 of retinal area), and a 3.8-fold increase in the number of arteriolar microthromboses (SHR diabetic 23,504 +/- 5523 microns2 vs SHR non-diabetic 6228 +/- 2707 microns2). Aminoguanidine treatment of SHR diabetic rats reduced the number of acellular capillaries by 50%, and completely prevented both arteriolar deposition of PAS-positive material and abnormal microthrombus formation. These data suggest that hypertension-induced deposition of glycated proteins in the retinal vasculature plays a central role in the acceleration of diabetic retinopathy by hypertension.
Hammes
H P
HP
Third Medical Department, of Justus-Liebig-University of Giessen, Germany.
Brownlee
M
M
Edelstein
D
D
Saleck
M
M
Martin
S
S
Federlin
K
K
D000783:Aneurysm / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000032:analysis; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012171:Retinal Vessels / Q000473:pathology* / Q000503:physiopathology; D013045:Species Specificity
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine