Arterial hypertension exacerbates oxidative stress in early diabetic retinopathy

Abstract

The present study was undertaken to investigate the redox status in the retina of an experimental model that combines hypertension and diabetes. Spontaneously hypertensive rats (SHR) and their control Wystar Kyoto (WKY) rats were rendered diabetic and, after 20 days, the rats were sacrificed and the retinas collected. The superoxide production was higher in diabetic than in control WKY (p < 0.03) and SHR rats showed elevated superoxide production compared with WKY groups (p < 0.009). The glutathione antioxidant system was diminished only in diabetic SHR (p < 0.04). Tirosyne nitration was higher in diabetic WKY and control SHR compared with control WKY (p < 0.03), and further increment was observed in diabetic SHR (p < 0.02). The DNA damage estimated by immunohystochemistry for 8-OHdG was higher in control SHR than in WKY, mainly in diabetic SHR (p < 0.0001). Hypertension aggravates oxidative-induced cytotoxicity in diabetic retina due to increasing of superoxide production and impairment of antioxidative system.

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

“…2,3 In addition, the results of United Kingdom Prospective Diabetes Study have clearly demonstrated the benefit of blood pressure control for hypertension in type 2 diabetic patients in terms of reducing risk for both deterioration of retinopathy and visual acuity. 4 This result is supported by experimental studies with spontaneously hypertensive rats, rendered diabetic by streptozotocin (STZ), which have demonstrated that the concomitance of diabetes and hypertension leads to aggravated early inflammatory events, 5,6 oxidative stress, 7,8 neurodegeneration and mitochondrial dysfunction 8 in the retina. Notably, these effects can be reduced by antihypertensive drug treatment.…”

Green Tea Is Neuroprotective in Diabetic Retinopathy

“…Systolic blood pressure (SBP) was obtained by tail-cuff plethysmography (Physiograph MK-III-S; Narco Bio-System, Houston, TX) as previously reported. 26 Twelve weeks after the induction of diabetes (DM), the rats were submitted to electroretinography and then euthanized, at which point the retinas were collected. We chose to use diabetic SHR because it has previously been shown that these rats displayed earlier and more severe retinal lesions than their normotensive counterparts, diabetic WKY, 27,28 and also because hypertension is frequently present in diabetic individuals with retinopathy.…”

The contribution of hypertension to diabetic nephropathy and retinopathy: the role of inflammation and oxidative stress

“…84 In the retina, a number of studies have shown that there is an increase in oxidative markers after the induction of DM, 67,[93][94][95] but the concomitance of diabetes and hypertension evoked earlier oxidative retinal damage characterized by an increase in nitrotyrosine and 8-OHdG in retinal tissue from short-term STZ-induced DM in SHRs. [96][97][98][99] These oxidative markers were the consequence of an increase in superoxide production and depletion of the gluthationereduced antioxidant system in the retinal tissue. [96][97][98] Interestingly, the administration of a superoxide dismutase mimetic tempol to diabetic SHRs re-established the redox status and improved early molecular markers of DR. 97 In these models, with long-term diabetes (12 weeks of duration), we have demonstrated that hypertension could account for exacerbation of retinopathy in diabetic SHRs.…”

“…[96][97][98][99] These oxidative markers were the consequence of an increase in superoxide production and depletion of the gluthationereduced antioxidant system in the retinal tissue. [96][97][98] Interestingly, the administration of a superoxide dismutase mimetic tempol to diabetic SHRs re-established the redox status and improved early molecular markers of DR. 97 In these models, with long-term diabetes (12 weeks of duration), we have demonstrated that hypertension could account for exacerbation of retinopathy in diabetic SHRs. It was observed that higher levels of apoptotic neural cells were found in retinas from diabetic SHR, accompanied by increased glial reaction, both of which are accepted as early markers of DR.…”