Masai M, Fujioka Y, Fujiwara M, Morimoto S, Miyoshi A, Suzuki H, Iwasaki T
Hyogo College of Medicine, 1-1, Mukugawa-cho, Nishinomiya, 663-8501, Japan.
Eur J Clin Invest. 2001 Mar;31(3):193-200.
Activation of Na+/H+ exchanger (NHE) is known to be related to elevated blood pressure in hyperinsulinemia. To test whether there is the change in NHE activity in insulin resistance, we measured NHE activity of platelets in fructose-induced hyperinsulinemia in Wistar-Kyoto rats (WKY), in borderline hypertensive rats (BHR), and in spontaneously hypertensive rats (SHR). All rats were fed a 60% fructose diet for 4 weeks to induce hyperinsulinemia and hypertriglyceridemia. Intracellular pH (pHi) was measured with a pH-sensitive fluorescent dye 2'7'-bis (2-carboxyethyl)-5-carboxyfluorescein acetoxymethyl ester. NHE activity was evaluated by the recovery of pHi following addition of sodium propionate (Vmax). Measurement of intracellular calcium ([Ca2+]i) was performed using fura2/acetoxymethylester. Systolic blood pressure in fructose diet BHR elevated significantly greater than that in control diet BHR with the increase of both [Ca2+]i and Vmax. In WKY, there was no significant increase in systolic blood pressure and [Ca2+]i except Vmax in a fructose diet. Vmax in control diet SHR was greater than in control diet WKY and BHR, and we found no additional increase in Vmax with a fructose diet in SHR. In BHR, a high salt diet increased systolic blood pressure and Vmax to a similar degree as a fructose diet or a high salt combined with a fructose diet. Plasma insulin concentration correlated positively with Vmax in WKY and BHR, but not SHR. A fructose diet induces hyperinsulinemia and elevates blood pressure in BHR. Hyperinsulinemia appears to activate NHE in a different manner in SHR, and might be associated with an elevation in blood pressure in BHR.
已知钠氢交换体（NHE）的激活与高胰岛素血症时血压升高有关。为了检测胰岛素抵抗时NHE活性是否发生变化，我们测量了Wistar-Kyoto大鼠（WKY）、临界高血压大鼠（BHR）和自发性高血压大鼠（SHR）在果糖诱导的高胰岛素血症状态下血小板的NHE活性。所有大鼠均喂食60%果糖饮食4周以诱导高胰岛素血症和高甘油三酯血症。用pH敏感荧光染料2'7'-双（2-羧乙基）-5-羧基荧光素乙酰氧基甲酯测量细胞内pH（pHi）。通过添加丙酸钠后pHi的恢复情况（Vmax）评估NHE活性。使用fura2/乙酰氧基甲酯测量细胞内钙（[Ca2+]i）。随着[Ca2+]i和Vmax的增加，果糖饮食组BHR的收缩压升高幅度显著大于对照饮食组BHR。在WKY中，果糖饮食除了Vmax外，收缩压和[Ca2+]i没有显著增加。对照饮食组SHR的Vmax大于对照饮食组WKY和BHR，并且我们发现SHR在果糖饮食后Vmax没有进一步增加。在BHR中，高盐饮食使收缩压和Vmax升高的程度与果糖饮食或高盐联合果糖饮食相似。血浆胰岛素浓度在WKY和BHR中与Vmax呈正相关，但在SHR中并非如此。果糖饮食可诱导BHR出现高胰岛素血症并升高血压。高胰岛素血症似乎以不同方式激活SHR中的NHE，并且可能与BHR血压升高有关。
