Zenner Zachary P, Gordish Kevin L, Beierwaltes William H
Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA.
Integr Blood Press Control. 2017 Dec 19;11:1-9. doi: 10.2147/IBPC.S147674. eCollection 2018.
We have previously reported that a moderate dietary supplementation of 20% fructose but not glucose leads to a salt-sensitive hypertension related to increased proximal sodium-hydrogen exchanger activity and increased renal sodium retention. We also found that while high salt increased renal nitric oxide formation, this was retarded in the presence of fructose intake. We hypothesized that at least part of the pathway leading to fructose-induced salt-sensitive hypertension could be due to fructose-induced formation of reactive oxygen species and inappropriate stimulation of renin secretion, all of which would contribute to an increase in blood pressure. We found that both 20% fructose intake and a high-salt diet stimulated 8-isoprostane excretion. The superoxide dismutase (SOD) mimetic tempol significantly reduced this elevated excretion. Next, we placed rats on a high-salt diet (4%) for 1 week in combination with normal rat chow or 20% fructose with or without chronic tempol administration. A fructose plus high-salt diet induced a rapid increase (15 mmHg) in systolic blood pressure and reversed high salt suppression of plasma renin activity. Tempol treatment reversed the pressor response and restored high salt suppression of renin. We conclude that fructose-induced salt-sensitive hypertension is driven by increased renal reactive oxygen species formation associated with salt retention and an enhanced renin-angiotensin system.
我们之前曾报道，饮食中适度补充20%的果糖而非葡萄糖会导致与近端钠氢交换体活性增加及肾钠潴留增多相关的盐敏感性高血压。我们还发现，虽然高盐会增加肾脏一氧化氮的生成，但在摄入果糖的情况下，这一过程会受到抑制。我们推测，导致果糖诱导的盐敏感性高血压的至少部分途径可能是由于果糖诱导的活性氧生成以及肾素分泌的不适当刺激，所有这些都会导致血压升高。我们发现，摄入20%的果糖和高盐饮食都会刺激8-异前列腺素的排泄。超氧化物歧化酶（SOD）模拟物tempol可显著降低这种升高的排泄。接下来，我们将大鼠置于4%的高盐饮食中1周，同时给予正常大鼠饲料或20%的果糖，有无长期给予tempol。果糖加高盐饮食导致收缩压迅速升高（15 mmHg），并逆转了高盐对血浆肾素活性的抑制。Tempol治疗可逆转升压反应，并恢复高盐对肾素的抑制。我们得出结论，果糖诱导的盐敏感性高血压是由与钠潴留相关的肾脏活性氧生成增加以及肾素-血管紧张素系统增强所驱动的。
