Citrus flavonoid naringenin improves aortic reactivity in streptozotocin-diabetic rats

Abstract

Background and objective: Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of naringenin was investigated on aortic reactivity of streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Male diabetic rats (n=32) were divided into control, naringenin-treated control, diabetic, and naringenin-treated diabetic groups of eight animals each. The latter group received naringenin for 5 weeks at a dose of 10 mg/kg/day after diabetes induction. The contractile responses to potassium chloride (KCl) and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Meanwhile, participation of nitric oxide (NO) and endothelial vasodilator factors in response to ACh were evaluated using N (G)-nitro-l-arginine methyl ester (L-NAME) and indomethacin (INDO), respectively.

Results: Maximum contractile response of endothelium-intact rings to KCl and PE was significantly (P<0.05) lower in naringenin-treated diabetic rats as compared to untreated diabetics. Endothelium-dependent relaxation to ACh was significantly (P<0.05-0.01) higher in naringenin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester (L-NAME) significantly (P<0.001) attenuated the observed response.

Conclusion: Chronic treatment of diabetic rats with naringenin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and endothelium integrity is necessary for this beneficial effect.

Keywords: Aorta; diabetes mellitus; naringenin; streptozotocin.

Figure 1

Comparison of body weight and serum glucose level in diabetic rats treated with naringenin (means ± S.E.M) (n=8). *P<0.05, **P<0.01, ***P<0.005, ****P<0.0005 (as compared to week 0 in the same group) $ P<0.05, $$P<0.01, $$$P<0.005 (vs. Diabetic in the same week).

Figure 2

Cumulative concentration-response curves for KCl (a) and phenylephrine (PE) (b) in aortic preparations 6 weeks after experiment (means ± S.E.M). *P<0.05, **P<0.01 (As compared to control), #P<0.05 (as compared to diabetic), $ P<0.05 (as compared to control).

Figure 3

Cumulative concentration-response curves for ACh in aortic rings precontracted with PE. *P<0.05, **P<0.01 (as compared to diabetic), $ P<0.05 (as compared to control).

Figure 4

Maximum relaxation response for ACh in aortic rings precontracted with phenylephrine in the presence and absence of L-NAME. *P<0.05, **P<0.01, ***P<0.005 (vs. control), # P<0.05, ## P<0.01 (vs. diabetic), $ P<0.05 (vs. diabetic + L-NAME).

Figure 5

Maximum relaxation response for ACh in aortic rings precontracted with phenylephrine in the presence and absence of indomethacin. *P<0.05 (vs. control), # P<0.05 (vs. diabetic).