Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with l-NAME-induced hypertension
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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.
KeywordsCurcumin Tetrahydrocurcumin Vascular dysfunction l-NAME hypertension Nitric oxide Oxidative stress
This study was supported by Thailand Research Fund (Grant No. DBG 5380045) and a grant from National Research University of Thailand, Khon Kaen University. Saowanee Nakmareong was supported by a CHE-PhD Scholarship, Commission on Higher Education, Ministry of Education, Thailand. The authors thank Professor Stephen E. Greenwald, Queen Mary University of London, for language editing of the manuscript and valuable suggestions.
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