August 16, 2016Open Access

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension

AGAlfredo GamboaUnited States Nuclear Regulatory Commission RFRocío FigueroaClinica Universidad de Navarra SPSachin Y. ParanjapeVanderbilt University Medical Center

Structured PICO

Does autonomic blockade improve NO-mediated vasodilation in obese hypertensive subjects?

Population

14 obese hypertensive subjects (BMI between 30 and 40 kg/m2), mean age 49±3.6 years, mean BMI 34±1 kg/m2, mean BP 165/94±7/6 mm Hg.

Intervention

Autonomic blockade (trimethaphan 4 mg/min IV) with intrabrachial acetylcholine (10, 30, and 50 μg/min) and sodium nitroprusside (1, 2, and 3 μg/min)

Comparator

Intact day (no autonomic blockade) with intrabrachial acetylcholine and sodium nitroprusside

Outcome

Forearm blood flow response to intrabrachial acetylcholine (NO-mediated vasodilation) compared with sodium nitroprusside (endothelial-independent vasodilation)surrogate

Autonomic blockade restores NO-mediated vasodilation in obese hypertensive patients, suggesting sympathetic activation drives endothelial dysfunction in this population.

Abstract

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.

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