Adiponectin replenishment ameliorates obesity-related hypertension
Adiponectin replenishment ameliorates obesity-related hypertension
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DOI：
10.1161/01.hyp.0000222368.43759.a1
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发表时间：
2006-06-01
期刊：
影响因子：
8.3
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Ohashi, Koji;Kihara, Shinji;Shimomura, Iichiro
肥胖患者易患高血压。我们已经报道了肥胖者血浆脂联素水平降低，脂联素具有许多防御肥胖相关疾病的特性，如2型糖尿病和冠状动脉疾病。本研究旨在探讨脂联素与小鼠高血压的关系。通过颈动脉导管直接测量血压和心率，通过尾动脉自动血压计间接测量血压和心率。肥胖KKAy小鼠在21周龄时血浆脂联素水平显著低于对照C57 BL/6 J小鼠，收缩压显著高于对照C57 BL/6 J小鼠。腺病毒携带的脂联素显著降低KKAy小鼠的血压。采用脂联素基因敲除（KO）小鼠，研究了脂联素在无胰岛素抵抗状态下对血压调节的直接作用。脂联素基因敲除小鼠在高盐饮食（8%NaCl）下无胰岛素抵抗时发生高血压。盐饲脂联素基因敲除小鼠的高血压与主动脉内皮型一氧化氮合酶（eNOS）和前列腺素I-2合酶mRNA水平降低以及血浆内皮型一氧化氮合酶和前列腺素I-2合酶代谢产物水平降低有关。脂联素治疗降低了升高的血压，并将上述mRNA水平校正至野生型水平。我们的研究结果表明，低脂联素血症有助于肥胖相关的高血压的发展，至少部分，直接，除了其通过胰岛素抵抗的影响，脂联素治疗可能是潜在的有用的代谢综合征患者的高血压。
Patients with obesity are susceptible to hypertension. We have reported that the plasma adiponectin levels are decreased in obesity and that adiponectin has many defensive properties against obesity-related diseases, such as type 2 diabetes and coronary artery disease. The aim of this study was to determine the relationship between adiponectin and hypertension in mice. We measured blood pressure and heart rate directly by a catheter in the carotid artery and indirectly by automatic sphygmomanometer at the tail artery. Obese KKAy mice had significantly lower plasma adiponectin levels and higher systolic blood pressure than control C57BL/6J mice at 21 weeks of age. Adenovirus-elivered adiponectin significantly decreased blood pressure in KKAy mice. The direct role of adiponectin on blood pressure regulation under insulin resistance-free state was investigated in adiponectin-knockout (KO) mice. Adiponectin KO mice developed hypertension when maintained on a high-salt diet (8% NaCl) without insulin resistance. The hypertension of salt-fed adiponectin KO mice was associated with reduced mRNA levels of endothelial NO synthase (eNOS) and prostaglandin I-2 synthase in aorta and low metabolite levels of endothelial NO synthase and prostaglandin I2 synthase in plasma. Adiponectin therapy lowered the elevated blood pressure and corrected the above mRNA levels to those of the wild type. Our results suggest that hypoadiponectinemia contributes to the development of obesity-related hypertension, at least in part, directly, in addition to its effect via insulin resistance, and that adiponectin therapy can be potentially useful for hypertension in patients with the metabolic syndrome.