Combination of Captopril and Allopurinol Retards Fructose-Induced Metabolic Syndrome

Abstract

Background: Both ACE inhibitors and allopurinol have been shown to partially prevent metabolic syndrome induced by fructose. We tested the hypothesis that combined therapy might be more effective at blocking the metabolic syndrome induced with fructose. Methods: Male Sprague-Dawley rats were fed a high fructose diet with or without allopurinol, captopril, or the combination for 20 weeks. A control group received a normal diet. All groups were pair-fed to assure equivalent caloric intake. Results: Despite reduced energy intake, the fructose-fed rats developed features of metabolic syndrome including elevated blood pressure, abdominal obesity, hypertriglyceridemia, hyperuricemia and hyperinsulinemia. While both allopurinol and captopril alone tended to reduce features of the metabolic syndrome, the combined therapy was synergistic, with significant reduction in blood pressure, less accumulation of abdominal fat, an improvement in the dyslipidemia and a complete prevention of insulin resistance. Conclusion: A high fructose diet can induce metabolic syndrome even in the setting of caloric restriction. Captopril and allopurinol synergistically reduce features of the metabolic syndrome, especially hypertension, insulin resistance and dyslipidemia. Combination allopurinol and ACE inhibitor therapy might provide a superior means to prevent diabetes and cardiovascular disease.

Comparing the Effects of Inorganic Nitrate and Allopurinol in Renovascular Complications of Metabolic Syndrome in Rats: Role of Nitric Oxide and Uric Acid

“…This could be attributed to the effect of sodium nitrate in inducing nitric oxide-like bioactivity in humans including a robust reduction in blood pressure, inhibition of platelet aggregation and improvement of endothelial function [15,20,33]. On the other hand, and in accordance with our study, it was found that allopurinol had a partial effect in preventing the rise Comparing the effects of inorganic nitrate and allopurinol in renovascular complications of metabolic syndrome in rats: role of nitric oxide and uric acid in arterial blood pressure when compared to captopril, a potent antihypertensive drug [22]. However, allopurinol was a potent drug in reducing both the hyperuricemia and the increase in the adipose tissue index induced by the metabolic syndrome compared to the effect of sodium nitrate.…”

“…Features of the syndrome were in the form of hypertension, hyperuricemia and hyperinsulinemia in accordance with Roncal et al [22].…”

“…Blood pressure was measured at baseline, at 4 weeks and at 10 weeks. The mean of three successive measurements was taken [22].…”

Response to Dr White

“…Experimental studies have also documented that fructose is distinct from glucose in its ability to induce metabolic syndrome and that this is independent of energy intake. 5,6 These data are consistent with a recent meta-analysis that found that high-fructose corn syrup-containing beverages increase the risk for metabolic syndrome and diabetes. 7 Our finding that we induced metabolic syndrome in 25% of adults within 2 weeks is of great concern.…”

Role of Nitric Oxide Synthase Uncoupling at Rostral Ventrolateral Medulla in Redox-Sensitive Hypertension Associated With Metabolic Syndrome

“…34 Extension of HFD feeding to 12 (J.Y.H. Chan et al, unpublished data, 2014) or 20 weeks 47 also did not cause a significant increase in body weight. We therefore reason that it is unlikely that the relationship between oxidative stress in RVLM and development of hypertension in this HFD model of MetS is obesity-dependent.…”