Comparing the effects of inorganic nitrate and allopurinol in renovascular complications of metabolic syndrome in rats: role of nitric oxide and uric acid

Introduction: The epidemic of metabolic syndrome is increasing worldwide and correlates with elevation in serum uric acid and marked increase in total fructose intake. Fructose raises uric acid and the latter inhibits nitric oxide bioavailability. We hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome and treatment of hyperuricemia or increased nitric oxide may improve it. Material and methods: Two experiments were performed. Male Sprague-Dawley rats were fed a control diet or a high-fructose diet to induce metabolic syndrome. The latter received either sodium nitrate or allopurinol for 10 weeks starting with the 1st day of fructose to evaluate the preventive role of the drugs or after 4 weeks to evaluate their therapeutic role. Results: A high-fructose diet was associated with significant (p < 0.05) hyperuricemia (5.9+/-0.5 mg/dl, hypertension (125.2+/-7.8 mm Hg), dyslipidemia and significant decrease in tissue nitrite (27.4+/-2.01 mmol/l). Insulin resistance, as manifested by HOMAIR (20.6+/-2.2) and QUICKI (0.23+/-0.01) indices, as well as adiposity index (12.9+/-1.1) was also significantly increased (p < 0.1). Sodium nitrate or allopurinol was able to reverse these features significantly (p < 0.05) in the preventive study better than the therapeutic study. Conclusions: Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. Either sodium nitrate or allopurinol can prevent this pathological condition by different mechanisms of action.