The angiotensin II receptor antagonist candesartan cilexetil (TCV-116) ameliorates retinal disorders in rats.
OBJECTIVE
The results of the EUCLID trial (EURODIAB Controlled Trial of Lisinopril in Insulin-dependent Diabetes Mellitus) highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. Candesartan cilexetil (TCV-116), a potent angiotensin II (AII) receptor antagonist, has beneficial effects on hypertension as well as on heart, renal and cerebrovascular disease. We aimed to evaluate the effectiveness of candesarten cilexetil in ameliorating retinal disorders induced by hyperglycaemia.


METHODS
We compared retinal vascular endothelial growth factor (VEGF) mRNA expression and the latencies of retinal oscillatory potentials in TCV-116-treated and control groups of stroke-prone spontaneously hypertensive rats with streptozocin (STZ)-induced diabetes.


RESULTS
Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated spontaneously hypertensive rats compared with a non-treated spontaneously hypertensive rat group matched for age. These changes were dependent on hyperglycaemia but independent of hypertension. Treatment with TCV-116 (3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potential peaks, but had no effect on plasma glucose concentrations.


CONCLUSIONS
These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages.
Nagisa
Y
Y
Pharmaceutical Research Division, Takeda Chemical Industries, Osaka, Japan. Nagisa_Yasutaka@takeda.co.jp
Shintani
A
A
Nakagawa
S
S
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D016228:Endothelial Growth Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D008222:Lymphokines / Q000235:genetics; D008297:Male; D009991:Oscillometry; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D016228:Endothelial Growth Factors; D008222:Lymphokines; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C077793:candesartan cilexetil