Curcumin Mitigates Hypertension, Endothelial Dysfunction and Oxidative Stress in Rats with Chronic Exposure to Lead and Cadmium.

Lead (Pb) and cadmium (Cd) are environmental pollutants and nonessential elements in the body. Both metals induce the development of hypertension which is associated with oxidative stress. Curcumin (CUR) is a polyphenolic compound with strong antioxidant activity. The present study evaluated the effect of CUR on oxidative stress, alteration of vascular responsiveness and hypertension induced by exposure to either Pb, Cd or the combination of Pb and Cd. Male Sprague-Dawley rats were exposed to low level of lead acetate (100 mg/L) and/or cadmium chloride (10 mg/L) in the drinking water for 16 weeks. The control animals received deionized water as drinking water. CUR (100 mg/kg) or propylene glycol as vehicle was intragastrically administered once daily for the last 4 weeks. Exposure to Pb, Cd or the combination induced increases in blood pressure and peripheral vascular resistance, and decreased the blood pressure response to intravenous infusion to acetylcholine. Supplementation with CUR significantly reduced blood pressure, alleviated oxidative stress, and increased plasma nitrate/nitrite and glutathione in the blood. The effects of CUR were associated with the improvement of vascular responsiveness, upregulation of the endothelial nitric oxide synthase and downregulation of the NADPH oxidase expression. Furthermore, CUR reduced the metal levels in blood, aorta, liver and kidney. Altogether, exposure to the combination of Pb and Cd aggravated hypertension and oxidative stress, and CUR effectively ameliorated these adverse events in metal exposed animals. Data indicate that CUR may be useful as a dietary supplement for protection against the noxious effects of the heavy metals.

Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensinⅡ, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensinⅡlevels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.