自主神经阻滞可逆转肥胖相关性高血压中的内皮功能障碍。
Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.
作者信息
Gamboa Alfredo, Figueroa Rocío, Paranjape Sachin Y, Farley Ginnie, Diedrich Andre, Biaggioni Italo
机构信息
From the Division of Clinical Pharmacology (A.G., R.F., S.Y.P., G.F., A.D., I.B.), Departments of Medicine (A.G., R.F., S.Y.P., G.F., A.D., I.B.), and Pharmacology (I.B.), Vanderbilt University, Nashville, TN.
出版信息
Hypertension. 2016 Oct;68(4):1004-10. doi: 10.1161/HYPERTENSIONAHA.116.07681. Epub 2016 Aug 15.
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 with 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 to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30<body mass index<40 kg/m(2)). Acetylcholine and sodium nitroprusside were given at equipotent doses (10, 30, and 50 μg/min and 1, 2, and 3 μg/min, respectively) to 14 obese subjects (49±3.6 years, 34±1 kg/m(2), 165/94±7/6 mm Hg), on separate occasions 1 month apart, randomly assigned. Autonomic blockade increased basal forearm blood flow (from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute, P=0.078). As expected, NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation; forearm blood flow 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/100 mL per minute with the highest dose of acetylcholine, P<0.05. In contrast, forearm blood flow 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/100 mL per minute 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-associated hypertension and provides further rationale to explore it as a therapeutic target.
一氧化氮（NO）介导的血管舒张功能受损（内皮功能障碍）与肥胖相关，被认为是高血压发生发展的一个因素。我们之前发现，在自主神经阻断过程中，与健康对照相比，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NO介导的血管舒张功能受损继发于交感神经激活。我们通过测定自主神经阻断（三甲噻方4 mg/min静脉注射）对肥胖高血压患者（体重指数30<体重指数<40 kg/m²）中NO介导的血管舒张（前臂血流量因肱动脉内注射乙酰胆碱而增加）与非内皮依赖性血管舒张（肱动脉内注射硝普钠）的影响，来验证这一假设。分别在相隔1个月的不同时间，将乙酰胆碱和硝普钠以等效剂量（分别为10、30和50 μg/min以及1、2和3 μg/min）给予14名肥胖受试者（49±3.6岁，34±1 kg/m²，165/94±7/6 mmHg），随机分配。自主神经阻断使基础前臂血流量增加（从3.9±0.7增至5.2±1.2 mL/100 mL每分钟，P = 0.078）。正如预期的那样，与非NO依赖性血管舒张相比，在未进行自主神经阻断时，NO介导的血管舒张受到抑制；最高剂量硝普钠使前臂血流量从3.6±0.6增至10.1±1.1 mL/100 mL每分钟，而最高剂量乙酰胆碱仅使其从3.7±0.4增至7.2±0.8 mL/100 mL每分钟，P<0.05。相比之下，自主神经阻断恢复了前臂对乙酰胆碱的血流反应，且与硝普钠的反应不再有差异（分别从6.2±1.1增至11.4±1.6 mL/100 mL每分钟以及从5.2±0.9增至12.5±0.9 mL/100 mL每分钟，P = 0.58）。我们的结果支持这样的观点，即交感神经激活导致了肥胖相关性高血压中所见的NO介导的血管舒张功能受损，并为将其作为治疗靶点进行探索提供了进一步的理论依据。
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