Involvement of angiotensin II-dependent vascular endothelial growth factor gene expression via NADPH oxidase in the retina in a type 2 diabetic rat model.
OBJECTIVE
To clarify the involvement of angiotensin II-dependent vascular endothelial growth factor (VEGF) via NADPH oxidase in the retina in spontaneously diabetic Torii (SDT) rats, a type 2 diabetic rat model. In SDT rats, the plasma glucose level and angiotensin-converting enzyme (ACE) levels were measured, and effects of angiotensin II receptor blocker (ARB) and angiotensin II were also studied.


METHODS
We evaluated the age-dependent changes in the peripheral and ocular angiotensin II-forming systems in SDT rats at 15 (n = 8), 20 (n = 8), 30 (n = 7), and 50 weeks of age (n = 8). We also evaluated the effect of an ARB (2.5 mg/kg/day candesartan) or angiotensin II (500 ng/kg/min) on retinal gene expressions of VEGF and p22phox, a subunit of NADPH oxidase.


RESULTS
The plasma glucose level was significantly increased from 20 weeks of age. No significant changes in ACE activities in the plasma, aorta, and eye were observed until 30 weeks of age. At 50 weeks, ACE activity in the eyes was significantly increased, whereas ACE activities in the plasma and aorta were not. At 50 weeks, significant increases in VEGF and p22phox, an NADPH oxidase subunit, were significantly reduced by candesartan. Angiotensin II infusion resulted in significant increases in VEGF and p22phox levels.


CONCLUSIONS
Angiotensin II is involved in the gene expression of VEGF via NADPH oxidase in the retina of SDT rats.
Fukumoto
Masanori
M
Department of Pharmacology, Osaka Medical College, Osaka, Japan.
Takai
Shinji
S
Ishizaki
Eisuke
E
Sugiyama
Tetsuya
T
Oku
Hidehiro
H
Jin
Denan
D
Sakaguchi
Masato
M
Sakonjo
Hiroshi
H
Ikeda
Tsunehiko
T
Miyazaki
Mizuo
M
D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D019255:NADPH Oxidases / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D012333:RNA, Messenger; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D007703:Peptidyl-Dipeptidase A; C081643:candesartan