Gordish Kevin L, Beierwaltes William H
Department of Physiology, Wayne State School of Medicine, Henry Ford Hospital, Detroit, MI, USA.
Department of Physiology, Wayne State School of Medicine, Henry Ford Hospital, Detroit, MI, USA; Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, USA.
Integr Blood Press Control. 2016 Jan 28;9:23-31. doi: 10.2147/IBPC.S96092. eCollection 2016.
Resveratrol is reported to reduce blood pressure in animal models of hypertension, but the mechanisms are unknown. We have shown that resveratrol infusion increases sodium excretion. We hypothesized that chronic ingestion of resveratrol would reduce angiotensin II (Ang II)-induced increases in blood pressure by decreasing oxidative stress and by also decreasing sodium reabsorption through a nitric oxide-dependent mechanism. We infused rats with vehicle or 80 μg Ang II/d over 4 weeks. Vehicle or Ang II-infused rats were individually housed, pair fed, and placed on a diet of normal chow or normal chow plus 146 mg resveratrol/d. Groups included 1) control, 2) resveratrol-fed, 3) Ang II-treated, and 4) Ang II plus resveratrol. Systolic blood pressure was measured by tail cuff. During the 4th week, rats were placed in metabolic caging for urine collection. NO2/NO3 and 8-isoprostane excretion were measured. Ang II increased systolic blood pressure in the 1st week by +14±5 mmHg (P<0.05) in Group 3 and +10±3 mmHg (P<0.05) in Group 4, respectively. Blood pressure was unchanged in Groups 1 and 2. After 4 weeks, blood pressure remained elevated in Group 3 rats with Ang II (+9±3 mmHg, P<0.05), but in Group 4, blood pressure was no longer elevated (+2±2 mmHg). We found no significant differences between the groups in sodium excretion or cumulative sodium balance (18.49±0.12, 17.75±0.16, 17.97±0.17, 18.46±0.18 μEq Na+/7 d in Groups 1-4, respectively). Urinary excretion of NO2/NO3 in the four groups was 1) 1631±207 μmol/24 h, 2) 1045±236 μmol/24 h, 3) 1490±161 μmol/24 h, and 4) 609±17 μmol/24 h. 8-Isoprostane excretion was 1) 63.85±19.39 nmol/24 h, 2) 73.57±22.02 nmol/24 h, 3) 100.69±37.62 nmol/24 h, and 4) 103.00±38.88 nmol/24 h. We conclude that chronic resveratrol supplementation does not blunt Ang II-increased blood pressure, and while resveratrol has mild depressor effects, these do not seem to be due to natriuresis or enhanced renal nitric oxide synthesis.
据报道，白藜芦醇可降低高血压动物模型的血压，但其机制尚不清楚。我们已经表明，输注白藜芦醇可增加钠排泄。我们假设，长期摄入白藜芦醇可通过降低氧化应激以及通过一氧化氮依赖性机制减少钠重吸收，从而降低血管紧张素II（Ang II）诱导的血压升高。我们给大鼠输注溶媒或每天80μg Ang II，持续4周。输注溶媒或Ang II的大鼠单独饲养，配对喂食，并给予普通饲料或普通饲料加每天146mg白藜芦醇的饮食。分组包括：1）对照组，2）喂食白藜芦醇组，3）Ang II治疗组，4）Ang II加白藜芦醇组。通过尾套法测量收缩压。在第4周，将大鼠置于代谢笼中收集尿液。测量NO2/NO3和8-异前列腺素排泄量。Ang II使第3组收缩压在第1周分别升高+14±5 mmHg（P<0.05），第4组升高+10±3 mmHg（P<0.05）。第1组和第2组血压无变化。4周后，第3组接受Ang II的大鼠血压仍升高（+9±3 mmHg，P<0.05），但在第4组，血压不再升高（+2±2 mmHg）。我们发现各组之间钠排泄或累积钠平衡无显著差异（第1 - 4组分别为18.49±0.12、17.75±0.16、17.97±0.17、18.46±0.18μEq Na+/7天）。四组中NO2/NO3的尿排泄量分别为：1）1631±207μmol/24小时，2）1045±236μmol/24小时，3）1490±161μmol/24小时，4）609±17μmol/24小时。8-异前列腺素排泄量分别为：1）63.85±19.39 nmol/24小时，2）73.57±22.02 nmol/24小时，3）100.69±37.62 nmol/24小时，4）103.00±38.88 nmol/24小时。我们得出结论，长期补充白藜芦醇不会减弱Ang II引起的血压升高，虽然白藜芦醇有轻度降压作用，但这些作用似乎不是由于利钠作用或增强的肾脏一氧化氮合成。
