Abstract 403: Autonomic Blockade Improves “Endothelial Dysfunction” in Obesity-Associated Hypertensive Human Subjects
Nitric oxide (NO) deficiency (“endothelial dysfunction”) is a hallmark of obesity and is thought to contribute to hypertension. In a previous study, however, we did not find differences in NO function between hypertensive and normotensive subjects if autonomic activity was removed with ganglionic blockade. We hypothesized, therefore, that sympathetic activation, known to occur in obesity hypertension, contributes to NO mediated endothelial dysfunction. To test this hypothesis we determined NO-mediated vasodilation (increase in forearm blood flow, FBF, to intrabrachial acetylcholine, ACh) and endothelial independent vasodilation (intrabrachial sodium nitroprusside, SNP) in obese hypertensive subjects (30<BMI<40 kg/m2) during intact and during autonomic blockade (trimethaphan 4 mg/min IV infusion). Seven obese subjects (49±3.6 years, 34±1 kg/m2, 165/94 ± 7/6 mm Hg) were studied on two separate occasions, one month apart, randomly assigned. As anticipated, autonomic blockade increased basal FBF (from 3.9±0.7 to 5.2±1.2 ml/100mL/min, p=0.078). As expected, NO-mediated vasodilation was blunted on the intact day: FBF increased from 3.6±0.6 to 10.1±1.1 with SNP, but only from 3.7±0.4 to 7.2±0.8 ml/100mL/min with ACh, p=0.047. In contrast, during autonomic blockade, FBF responses to SNP and ACh were similar (from 5.2±0.9 to 12.5±0.9 and from 6.2±1.1 to 11.4±1.6 ml/100mL/min, respectively, p= 0.578, figure). 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.
- © 2013 by American Heart Association, Inc.