Betulinic acid ameliorates endothelium-dependent relaxation in l-NAME-induced hypertensive rats by reducing oxidative stress

Fu, Jia-Yin; Qian, Ling-Bo; Zhu, Lie-Gang; Liang, Hao-Te; Tan, Yinuo; Lu, Haiyang; Lü, Jianfeng; Wang, Huiping; Xia, Qiang

doi:10.1016/j.ejps.2011.08.025

Cited by 54 publications

(36 citation statements)

References 48 publications

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“…Treatment of human endothelial cells with betulinic acid leads to phosphorylation of eNOS at serine 1177 and dephosphorylation of eNOS at threonine 495, and an increase in NO production [Hohmann N, Xia N, Forstermann U and Li H, unpublished data]. This is consistent with a recent report demonstrating that betulinic acid induces an endothelium-dependent, NO-mediated relaxation of isolated rat aorta [73].…”

Section: Betulinic Acidsupporting

confidence: 81%

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Li¹

2012

Recent Advances in Theories and Practice of Chinese Medicine

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Section: Betulinic Acidsupporting

confidence: 81%

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Li¹

2012

Recent Advances in Theories and Practice of Chinese Medicine

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“…Secondly, in the present study, we have not evaluated if the changes in SOD activity were induced by nitrite treatment or are a consequence of SBP reduction. Although previous studies have described similar results with other antihypertensive treatments (Fu et al 2011;Yang et al 2007;Amirkhizi et al 2010;Oktem et al 2011;Galisteo et al 2004), the precise molecular mechanisms associated with these changes in SOD activity remain to be determined. In summary, our results show for the first time that even a single daily oral dose of sodium nitrite exerts antioxidant effects and lowers SBP in 2K1C hypertension.…”

mentioning

confidence: 60%

“…As expected, we found decreased SOD and catalase activity in 2K1C hypertensive rats treated with vehicle, and the treatment with sodium nitrite restored SOD activity and induced a small increase in catalase activity in the 2K1C hypertensive rats (not statistically significant). Although we cannot rule out the possibility that nitrite affects SOD and catalase expression, we believe that these changes in SOD and catalase activities are consequences of reduced SBP found in 2K1C rats treated with nitrite, as previously described in different experimental models of hypertension (Fu et al 2011;Yang et al 2007;Amirkhizi et al 2010;Oktem et al 2011;Galisteo et al 2004). The improved activities of antioxidant enzymes (SOD and catalase) and the lower lipid peroxide levels and aortic DHE oxidation in 2K1C hypertensive rats treated with nitrite are consistent with the suggestion that nitrite treatment promotes relevant antioxidant effects, which contribute to antihypertensive effects here described.…”

mentioning

confidence: 69%

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension

Montenegro

Pinheiro

Amaral

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats. Sham-operated and 2K1C rats were treated with vehicle or sodium nitrite (15 mg/kg/day) for 4 weeks. We evaluated the effects induced by sodium nitrite treatment on systolic blood pressure (SBP) and NO markers such as plasma nitrite, nitrite + nitrate (NOx), cGMP, and blood levels of nitrosyl-hemoglobin. In addition, we also evaluated effects of nitrite on oxidative stress and antioxidant enzymes. Dihydroethidium (DHE) was used to evaluate aortic reactive oxygen species (ROS) production by fluorescence microscopy, and plasma levels of thiobarbituric acid-reactive species (TBARS) were measured in plasma samples from all experimental groups. Red blood cell superoxide dismutase (SOD) and catalase activity were evaluated with commercial kits. Sodium nitrite treatment reduced SBP in 2K1C rats (P < 0.05). We found lower plasma nitrite and NOx levels in 2K1C rats compared with normotensive controls (both P < 0.05). Nitrite treatment restored the lower levels of nitrite and NOx. While no change was found in the blood levels of nitrosyl-hemoglobin (P > 0.05), nitrite treatment increased the plasma levels of cGMP in 2K1C rats (P < 0.05). Higher plasma TBARS levels and aortic ROS levels were found in hypertensive rats compared with controls (P < 0.05), and nitrite blunted these alterations. Lower SOD and catalase activities were found in 2K1C hypertensive rats compared with controls (both P < 0.05). Nitrite treatment restored SOD activity (P < 0.05), whereas catalase was not affected. These data suggest that even a single daily oral dose of sodium nitrite is able to lower SBP and exert antioxidant effects in renovascular hypertension.

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“…Trans-resveratrol also prevents NOS3 uncoupling and lowers oxidative stress while preserving endothelial function (20), and it can up-regulate GTPCH-1 (252), suggesting multiple mechanisms whereby it may prove useful for treating NOS-opathy. Lastly, triterpenoids, such as betulinic acid isolated from birch tree bark, have been shown to improve endothelium-dependent relaxation in rats with L-NAME-induced hypertension by their ability to reduce oxidative stress (74). Betulinic acid may also up-regulate NOS3 expression and reduce NADPH oxidase expression in human endothelial cells through a PKC-dependent mechanism (209).…”

Section: Nos Activatorsmentioning

confidence: 99%

Nitric Oxide Synthases in Heart Failure

Carnicer

Crabtree

Sivakumaran

et al. 2013

Antioxidants & Redox Signaling

154

138

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Significance: The regulation of myocardial function by constitutive nitric oxide synthases (NOS) is important for the maintenance of myocardial Ca 2+ homeostasis, relaxation and distensibility, and protection from arrhythmia and abnormal stress stimuli. However, sustained insults such as diabetes, hypertension, hemodynamic overload, and atrial fibrillation lead to dysfunctional NOS activity with superoxide produced instead of NO and worse pathophysiology. Recent Advances: Major strides in understanding the role of normal and abnormal constitutive NOS in the heart have revealed molecular targets by which NO modulates myocyte function and morphology, the role and nature of posttranslational modifications of NOS, and factors controlling nitroso-redox balance. Localized and differential signaling from NOS1 (neuronal) versus NOS3 (endothelial) isoforms are being identified, as are methods to restore NOS function in heart disease. Critical Issues: Abnormal NOS signaling plays a key role in many cardiac disorders, while targeted modulation may potentially reverse this pathogenic source of oxidative stress. Future Directions: Improvements in the clinical translation of potent modulators of NOS function/dysfunction may ultimately provide a powerful new treatment for many hearts diseases that are fueled by nitroso-redox imbalance.

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Betulinic acid ameliorates endothelium-dependent relaxation in l-NAME-induced hypertensive rats by reducing oxidative stress

Cited by 54 publications

References 48 publications

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension

Nitric Oxide Synthases in Heart Failure

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