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Randomized Controlled Trial
. 2016 Oct;68(4):1004-10.
doi: 10.1161/HYPERTENSIONAHA.116.07681. Epub 2016 Aug 15.

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension

Alfredo Gamboa  1 , Rocío Figueroa  2 , Sachin Y Paranjape  2 , Ginnie Farley  2 , Andre Diedrich  2 , Italo Biaggioni  2
Affiliations
Randomized Controlled Trial

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension

Alfredo Gamboa et al. Hypertension. 2016 Oct.

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.

Keywords: autonomic nervous system; hypertension; nitric oxide; obesity; vasodilation.

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Conflict of interest statement

Conflict(s) of Interest/Disclosure(s): None

Figures

Figure 1
Figure 1. Study Design
Subjects were randomized to either the intact day (saline) or the blocked day (trimethaphan). The order of the vasodilators given (Acetylcholine, ACh; or sodium nitroprusside, SNP) was also randomize. Subjects were blinded as to which treatments were receiving each day.
Figure 2
Figure 2
Effect of increasing doses on sodium nitroprusside (SNP) or acetylcholine (Ach, x-axis) on forearm blood flow (FBF, y-axis) in obese hypertensive subjects studied on two separate occasions, during intravenous infusion of saline (intact autonomic nervous system, ANS, left panel) or the ganglionic blocker trimethaphan (TrMT, blocked ANS, right panel). FBF dilation to ACh was significantly decrease compared to SNP when the ANS was intact (*, p<0.05 by mixed effects model), but not if ANS was blocked by trimethaphan.
Figure 3
Figure 3
Panel A shows individual forearm blood flow (FBF) at baseline (Bsl), and the peak responses to acetylcholine (ACh, circles) and sodium nitroprusside (SNP, closed squares), during the intact (closed) and blocked (open) days. Panel B shows the change in FBF (peak minus saline or trimethaphan) for both ACh and SNP. The peak increase in FBF induced by these drugs was statistically significant between study days only for ACh (*, p<0.05 by Wilcoxon sign-rank test).
See this image and copyright information in PMC

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