J Clin Hypertens (Greenwich). 2010;12:117–124. ©2009 Wiley Periodicals, Inc.
The role of increased sympathetic nervous system (SNS) activity in the pathogenesis of obesity hypertension and insulin resistance is controversial. Eight dogs were instrumented and fed a high-fat diet (HFD) for 6 weeks. Dogs were evaluated for changes in weight, blood pressure, insulin resistance, and norepinephrine (NE) kinetics using a two-compartment model. The HFD resulted in weight gain, hypertension, and insulin resistance. During the 6 weeks of the HFD, although plasma NE concentration trended toward increasing (P=.09), SNS, assessed by NE kinetic studies, significantly increased (P=.009). Within 1 week of starting the HFD, NE release into the extravascular compartment (NE2) increased from 3.44±0.59 μg/mL to 4.87±0.80 μg/mL (P<.01) and this increase was maintained over the next 5 weeks of the HFD (NE2 at week 6 was 4.66±0.97 μg/mL). In addition to the increased NE2 there was also a significant increase in NE clearance (P=.04). There were significant correlations between the increase in NE2 and both the development of insulin resistance and hypertension. This study supports the hypothesis that activation of the SNS plays a pivotal role in the metabolic and hemodynamic changes that occur with weight gain induced by HFD.