Why the study?
Angiotensin II is implicated in diabetic retinopathy progression via vascular constriction and NADPH oxidase-mediated ROS formation, prompting investigation into whether angiotensin II receptor antagonism normalizes retinal changes.
Does candesartan improve retinal blood flow and reduce oxidative stress markers in a rat model of type 1 diabetes?
Does candesartan improve retinal blood flow and reduce oxidative stress markers in a rat model of type 1 diabetes?
Candesartan normalizes retinal blood flow and p22phox levels in a diabetic rat model, suggesting potential microvascular benefits in diabetic retinopathy.
Ang II receptor blockade may attenuate retinal oxidative stress in diabetic models; leaves open whether this prevents human retinopathy progression.
Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ). Eight weeks after the STZ injection, untreated diabetic rats were found to have a significant increase in tissue levels of angiotensin converting enzyme (ACE; p < 0.05) compared to non-diabetic controls, a 33% decrease in retinal blood flow rate (p < 0.001), and a dramatic increase in p22phox (a subunit of the NADPH oxidase). The decrease in retinal blood flow, and the increases in retinal ACE and p22phox in the diabetic rats, were all significantly attenuated (p < 0.05) by the administration of candesartan in drinking water within one week. Neither STZ nor candesartan induced any changes in tissue levels of superoxide dismutase (SOD-1), 4-hydroxynonenal (4-HNE), or nitrotyrosine. We conclude that one additional benefit of candesartan (and other angiotensin II antagonists) may be to normalize retinal blood flow, which may have clinical benefits in diabetic retinopathy.
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Eshaq et al. (2021) studied this question.
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