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Abstract Title:

Role of Resveratrol in Protecting Vasodilatation Function in Septic Shock Rats and its Mechanism.

Abstract Source:

J Trauma Acute Care Surg. 2019 Aug 5. Epub 2019 Aug 5. PMID: 31389921

Abstract Author(s):

Zi-Sen Zhang, Hong-Liang Zhao, Guang-Ming Yang, Jia-Tao Zang, Dan-Yang Zheng, Chen-Yang Duan, Lei Kuang, Yu Zhu, Yue Wu, Tao Li, Liang-Ming Liu

Article Affiliation:

Zi-Sen Zhang

Abstract:

BACKGROUND: Vascular dysfunction is a major cause of sepsis-induced multiple-organ dysfunction. Resveratrol is a polyphenol compound with extensive pharmacological effects including anti-inflammation. The aim of this study was to determine the role and mechanism of resveratrol in protecting vascular function following sepsis.

METHODS: The cecal ligation and puncture (CLP) method was used to establish a septic shock rat model. Resveratrol (5mg/kg and 10mg/kg) was administered intravenously immediately and at 12h after CLP, respectively. The effects of resveratrol on vasodilatation function, blood flow velocity, hemodynamics, and vital organ function and its relationship to Rac-1 and HIF-1α were observed.

RESULTS: Vascular relaxation reactivity and blood flow velocity were significantly decreased after septic shock, both were significantly improved by resveratrol 5mg/kg and 10mg/kg, and the effect of 10mg/kg was greater. The relaxation reactivity of the superior mesenteric artery (SMA) to acetylcholine (Ach) was increased by 43.2%. The blood flow velocity of mesenteric arterioles and venules was increased by 47.1% and 51%, respectively, after resveratrol (10mg/kg) administration compared with the septic shock group. The hemodynamics and both liver and kidney blood flow were significantly decreased after septic shock, which were significantly improved them by resveratrol, which enhanced the vascular relaxation reactivity in septic shock rats. The 72h survival rate of septic shock rats in the resveratrol group (62.5%) was significantly higher than that in the septic shock group (6.3%). Resveratrol significantly up-regulated the expression of eNOS and down-regulated the expression of iNOS, Rac-1 and HIF-1α. Inhibitors of Rac-1 and HIF-1α significantly improved the expression of eNOS, and inhibition of eNOS (L-NAME,5mg/kg) antagonized the resveratrol-induced improvement in vascular relaxation reactivity and survival.

CONCLUSION: Resveratrol was beneficial for vasodilatation function in rats with septic shock, which is the major contribution to resveratrol improving hemodynamics and organ perfusion. The mechanism involved resveratrol up-regulating the expression of eNOS by inhibiting Rac-1 and HIF-1α.

LEVEL OF EVIDENCE: therapeutic study, level II.

Study Type : Animal Study

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Sayer Ji
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