Inhibition of nitric oxide synthesis with N ( ω )-nitro-L-arginine methyl ester (L-NAME) induces marked hypertension and oxidative stress. Curcumin (CUR) has been shown strong antioxidant property. Tetrahydrocurcumin (THU), a major metabolite of CUR, possesses several pharmacological effects similar to CUR; however, it is less studied than CUR. We investigated whether CUR and THU could prevent vascular dysfunction and inhibit development of hypertension in L-NAME-treated rats. Male Sprague-Dawley rats were administered with L-NAME (50 mg/kg/day) in drinking water for 3 weeks. CUR or THU (50 and 100 mg/kg/day) was fed to animals simultaneously with L-NAME. L-NAME administration induced increased arterial blood pressure and elevated peripheral vascular resistance accompanied with impaired vascular responses to angiotensin II and acetylcholine. CUR and THU significantly suppressed the blood pressure elevation, decreased vascular resistance, and restored vascular responsiveness. The improvement of vascular dysfunction was associated with reinstating the marked suppression of eNOS protein expression in the aortic tissue and plasma nitrate/nitrite. Moreover, CUR and THU reduced vascular superoxide production, decreased oxidative stress, and increased the previously depressed blood glutathione (GSH) and the redox ratios of GSH in L-NAME hypertensive rats. The antihypertensive and some antioxidant effects of THU are apparently more potent than those of CUR. This study suggests that CUR and THU prevented the development of vascular dysfunction induced by L-NAME and that the effects are associated with alleviation of oxidative stress.

Oxidative stress plays a role in maintaining high arterial blood pressure and contributes to the vascular changes that lead to hypertension. Consumption of polyphenol-rich foods has demonstrated their beneficial role in the prevention and treatment of hypertension. Curcumin (CUR), a phenolic compound present in the rhizomes of turmeric, possesses cardiovascular protective, anti-inflammatory and antioxidant properties. The present study was designed to investigate the protective effect of CUR on 2kidney-1clip (2K-1C)-induced hypertension, endothelial dysfunction, vascular remodeling and oxidative stress in male Sprague-Dawley rats. Sham operated or 2K-1C rats were treated with CUR at a dose of 50 or 100 mg/kg/day (or vehicle). After 6 weeks of treatment, CUR ameliorated hemodynamic performance in 2K-1C hypertensive rats (P< 0.05), by reducing blood pressure, increasing hindlimb blood flow and decreasing hindlimb vascular resistance. Hemodynamic restoration was associated with a reduction in plasma angiotensin converting enzyme level. Endothelium-dependent vasorelaxation, in response to acetylcholine, of aortic rings isolated from 2K-1C hypertensive rats-treated with CUR was significantly increased (P< 0.05). CUR also attenuated hypertension-induced oxidative stress and vascular structural modifications. These effects were associated with elevated plasma nitrate/nitrite, upregulated eNOS expression, downregulated p47phox NADPH oxidase and decreased superoxide production in the vascular tissues. The overall findings of this study suggest the mechanisms responsible for the antihypertensive action of CUR in 2K-1C hypertension-induced endothelial dysfunction and vascular remodeling involve the improvement NO bioavailability and a reduction in oxidative stress.

Tetrahydrocurcumin (THC), a major metabolite of curcumin, possesses strong antioxidant and cardioprotective properties. However, the activities of THC in hypertension and its associated complications remain unknown. The aim of this study was to investigate the effect of THC on hemodynamic status, aortic elasticity and oxidative stress in rats with N-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Hypertension was induced in male Sprague-Dawley rats by administration of L-NAME (50 mg kg(-1) body weight) in drinking water for 5 weeks. THC at a dose of 50 or 100 mg kg(-1) per day was administered daily during the fourth and fifth weeks when the hypertensive state had been established. The effects of THC on hemodynamics, aortic elasticity, endothelial nitric oxide synthase (eNOS) protein expression and oxidative stress markers were assessed. Marked increases in blood pressure, peripheral vascular resistance, aortic stiffness and oxidative stress were found in rats after L-NAME administration. THC significantly reversed these deleterious effects by reducing aortic wall thickness and stiffness. These effects were associated with increased aortic eNOS expression, elevated plasma nitrate/nitrite, decreased oxidative stress with reduced superoxide production and enhanced blood glutathione. Our results provide the first evidence that THC attenuates the detrimental effect of L-NAME by improving the hemodynamic status and aortic elasticity concomitant with reduction of oxidative stress. The present study suggests that THC might be used as a dietary supplement to protect against cardiovascular alterations under nitric oxide-deficient conditions.

Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p < 0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p < 0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p < 0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

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