Gallic acid improves endothelium‐dependent vasodilatory response to histamine in the mesenteric vascular bed of diabetic rats

Background Endothelial dysfunction is one of the many complications caused by diabetes mellitus. The aim of the present study was to evaluate the effects of gallic acid ( GA ) on the mesenteric vascular bed ( MVB ) response to histamine in diabetic rats. Methods Forty male W istar rats were randomly assigned to a control group, an untreated alloxan‐induced diabetic group and three diabetic groups treated with different doses of GA . Six weeks after induction of diabetes and GA treatment, total antioxidant capacity ( TAC ), malondialdehyde ( MDA ) concentrations, and the vasodilatory response to histamine of the MVB (measured as changes in perfusion pressure) were determined. Results The vasodilatory response to histamine and TAC decreased, whereas MDA increased in the plasma from diabetic rats ( P  < 0.01). However, in the presence of 3 × 10 −5  mol/ L N G ‐nitro‐ l‐ arginine methyl ester (a nitric oxide synthase inhibitor) and 1 × 10 −5  mol/ L indomethacin (an inhibitor of prostaglandin production), the vasodilatory response of the MVB to histamine was reduced in all groups ( P  < 0.001). Treatment of diabetic rats with 20 and 40 mg/kg per day GA , but not 10 mg/kg per day GA , increased TAC and decreased MDA concentrations ( P  < 0.01 and P  < 0.001 vs untreated diabetic rats, respectively) and significantly improved the vasodilatory response to histamine ( P  < 0.05 and P  < 0.001, respectively). Conclusion The results show that, in diabetic rats, the endothelium‐dependent vasodilatory response of the MVB to histamine is significantly decreased and depends on both nitric oxide‐ and prostaglandin‐producing pathways and may be mediated by oxidative stress. Treatment with the antioxidant GA restored the vasodilatory response of the MVB to histamine.