Reduction of Inducible Nitric Oxide Synthase via Angiotensin Receptor Blocker Prevents the Oxidative Retinal Damage in Diabetic Hypertensive Rats

Abstract

Oral treatment with losartan reduces iNOS expression and reestablishes the redox status, thus ameliorating the early markers of DR in a model of diabetes and hypertension.

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

“…99 These findings indicate that the blockage of RAS exerts a variety of effects, including antioxidant, anti-apoptotic and anti-inflammatory properties. [98][99][100] Collectively, the above findings suggest that oxidative stress and inflammation may be common denominators of kidney and retinal damage in the concomitant presence of diabetes and hypertension (Figure 1). …”

“…Experimental and clinical studies have demonstrated that these maneuvers are also able to reduce superoxide generation and/or increase anti-oxidant defenses. 98,99,148,149 In this review, we have provided evidence that local generation of oxidative stress and inflammation can be a common mechanism of renal and retinal lesion in the presence of diabetes and hypertension. Although efficient, blood glucose control, normalization of arterial pressure and drugs that interfere in RAAS are currently unable to completely arrest diabetic renal and retinal diseases.…”

“…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.…”

“…Treatment with losartan re-established all of the above-mentioned parameters. 98 An AT1 receptor blockade with losartan also reduces retinal damage by decreasing inflammation and oxidative stress by means of a reduction in retinal inducible nitric oxide. 99 These findings indicate that the blockage of RAS exerts a variety of effects, including antioxidant, anti-apoptotic and anti-inflammatory properties.…”