Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.
Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.
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自主性封锁会逆转与肥胖相关的高血压中的内皮功能障碍。
DOI：
10.1161/hypertensionaha.116.07681
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Biaggioni I
中科院分区：
文献类型：
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作者：
Gamboa A;Figueroa R;Paranjape SY;Farley G;Diedrich A;Biaggioni I
受损的一氧化氮（NO）血管舒张（“内皮功能障碍”）与肥胖相关，并且被认为是高血压发展的一个因素。我们以前发现，在自主神经阻滞期间，与健康对照组相比，NO合成抑制在肥胖高血压患者中具有相似的升压作用，这表明受损的NO血管舒张继发于交感神经激活。我们在肥胖高血压患者（30<BMI<40 kg/m2）中通过测定自主神经阻滞（曲美沙芬4 mg/min IV）对NO介导的血管舒张（前臂血流量增加，FBF，肱内乙酰胆碱）的影响，与内皮非依赖性血管舒张（肱内硝普钠）进行比较，来验证这一假设。14名肥胖受试者（49±3.6岁，34±1 kg/m2，165/94 ± 7/6 mm Hg）在不同的时间间隔一个月，随机分配，以等效剂量（分别为10、30和50 mcg/min和1、2和3 mcg/min）给予乙酰胆碱和硝普钠。自主神经阻滞使基础FBF增加（从3.9±0.7 ml/100 mL/min增加至5.2±1.2 ml/100 mL/min，p=0.078）。正如预期的那样，与NO非依赖性血管舒张相比，一氧化氮介导的血管舒张在完整的一天减弱;最高剂量的硝普钠使FBF从3.6±0.6增加到10.1±1.1，但最高剂量的乙酰胆碱仅从3.7±0.4增加到7.2±0.8 ml/100 mL/min，p<0.05。相反，自主神经阻滞可恢复FBF对乙酰胆碱的反应，与硝普钠无差异（分别从6.2±1.1至11.4±1.6 ml/100 mL/min和从5.2±0.9至12.5±0.9，p= 0.58）。我们的研究结果支持了交感神经激活导致肥胖高血压中NO介导的血管舒张功能受损的概念，并为探索其作为治疗靶点提供了进一步的理论基础。
Impaired nitric oxide (NO) vasodilation (“endothelial dysfunction”) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared to healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow, FBF, to intrabrachial acetylcholine) compared to endothelial independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30<BMI<40 kg/m2). Acetylcholine and sodium nitroprusside were given at equipotent doses (10, 30 and 50 mcg/min and 1, 2 and 3 mcg/min, respectively) to 14 obese subjects (49±3.6 years, 34±1 kg/m2, 165/94 ± 7/6 mm Hg), on separate occasions one month apart, randomly assigned. Autonomic blockade increased basal FBF (from 3.9±0.7 to 5.2±1.2 ml/100mL/min, p=0.078). As expected, nitric oxide-mediated vasodilation was blunted on the intact day compared to NO-independent vasodilation; FBF increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside, but only from 3.7±0.4 to 7.2±0.8 ml/100mL/min with the highest dose of acetylcholine, p<0.05. In contrast, FBF responses to acetylcholine were restored by autonomic blockade, and were no longer different to nitroprusside (from 6.2±1.1 to 11.4±1.6 ml/100mL/min, and from 5.2±0.9 to 12.5±0.9 respectively, p= 0.58). Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity hypertension, and provides further rationale to explore it as a therapeutic target.