Valproic acid attenuates blood pressure, vascular remodeling and modulates ET-1 expression in L-NAME induced hypertensive rats

Thiyagarajan Rajeshwari, Boobalan Raja, Jeganathan Manivannan, Thangarasu Silambarasan
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引用次数: 12

Abstract

The present study was considered to assess the antihypertensive and antioxidant effect of valproic acid, against Nω- nitro-L arginine methyl ester hydrochloride (L-NAME) induced hypertension in male Wistar rats. Hypertension was prompted in adult male albino rats of the Wistar strain, weighing 180–220 g, by oral administration of the L-NAME (40 mg/kg body weight/day) in drinking water for 4 weeks. The L- NAME hypertensive rats revealed significant (P < 0.05) rise in the systolic and diastolic blood pressure, heart rate, water intake and heart weight L-NAME hypertensive rats also revealed significant (P < 0.05) increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides in plasma and tissues (heart and aorta), and significant (P < 0.05) drop in the body weight, nitrite and nitrate levels in plasma and aorta. Activities of enzymic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase in erythrocyte and tissues and the levels of non-enzymic antioxidant such as reduced glutathione in plasma and tissues, ET-1 mRNA expression in aorta was significantly (P < 0.05) increased in L-NAME rats. Valproic acid (VPA) supplementation (100 mg/kg) daily for four weeks brought back all the above parameters to near normal level. The above outcomes were confirmed by the histopathological examination. No significant (P < 0.05) effect was observed in control rats treated with valproic acid (100 mg/kg). These results suggest that valproic acid performed as an antihypertensive and antioxidant agent against L-NAME induced hypertension.

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丙戊酸对L-NAME诱导的高血压大鼠血压降低、血管重构及ET-1表达的调节作用
本研究旨在探讨丙戊酸对Nω-硝基- l精氨酸甲酯盐酸盐(L-NAME)致雄性Wistar大鼠高血压的降压和抗氧化作用。体重180 ~ 220 g的Wistar雄性成年白化大鼠,在饮水中口服L-NAME (40 mg/kg体重/天)4周,可引起高血压。L- NAME高血压大鼠P <L-NAME高血压大鼠的收缩压和舒张压、心率、摄水量和心重的升高也显示了显著的(P <0.05)血浆和组织(心脏和主动脉)中硫代巴比妥酸活性物质、脂质氢过氧化物水平升高,且显著(P <0.05)体重下降,血浆和主动脉亚硝酸盐和硝酸盐水平下降。红细胞和组织中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶等酶促抗氧化剂活性以及血浆和组织中还原性谷胱甘肽等非酶促抗氧化剂水平和主动脉中ET-1 mRNA表达均显著升高(P <0.05)升高。每天补充丙戊酸(VPA) 100 mg/kg,连续4周使上述各项指标恢复到接近正常水平。组织病理学检查证实了上述结果。无显著差异(P <丙戊酸(100 mg/kg)对对照大鼠的影响为0.05)。上述结果提示丙戊酸对L-NAME诱导的高血压具有抗高血压和抗氧化作用。
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