Effect of irbesartan on nitrotyrosine generation in non-hypertensive diabetic patients.

ABSTRACT

AIMS/HYPOTHESIS: Oxidative stress is involved in the pathogenesis of microangiopathic and macroangiopathic diabetic complications. The results of recent trials suggest that type 1 angiotensin II (AT-1) receptor blockers may prevent or delay nephropathy and cardiovascular disease in diabetic patients, independently of their anti-hypertensive action. There is evidence that AT-1 receptor blockers can work as intracellular antioxidants. This study investigated whether the AT-1 receptor blocker irbesartan is able to reduce nitrotyrosine formation in non-hypertensive diabetic patients under fasting conditions and during acute hyperglycaemia. METHODS: A total of 40 non-hypertensive, non-microalbuminuric Type 2 diabetic patients and 20 healthy, normotensive subjects were recruited for this study. Diabetic patients followed a randomised, double-blind, placebo-controlled, crossover protocol, taking either irbesartan (150 mg orally, twice daily) or placebo for 60 days. Fasting glucose and nitrotyrosine were measured at baseline and at the end of each treatment period. An OGTT was also performed at the same time intervals, during which plasma glucose and nitrotyrosine levels were monitored. RESULTS: Compared with baseline measurements, treatment with irbesartan (0.57+/-0.4 vs 0.35+/-0.3 micromol/l, p<0.01) but not placebo (0.58+/-0.3 vs 0.59+/-0.2 micromol/l) significantly reduced fasting nitrotyrosine levels. Irbesartan also significantly reduced nitrotyrosine formation during the OGTT. CONCLUSIONS/INTERPRETATION: . This study demonstrates that irbesartan reduces plasma levels of nitrotyrosine in diabetic patients and is effective in counterbalancing nitrotyrosine formation during acute hyperglycaemia. Our results may help to elucidate how AT-1 receptor blockers exert their beneficial effect independently of their BP-lowering activity.