C l i n i c a lA p p l i c a t i o n so fB a s i cR e s e a r c h
Serial Changes in Norepinephrine Kinetics
Associated With Feeding Dogs a High-Fat
Albert P. Rocchini, MD;1John Q. Yang, MD;1Marla J. Smith, BS;2
Mark A. Supiano, MD3,4
The role of increased sympathetic nervous system
(SNS) activity in the pathogenesis of obesity
hypertension and insulin resistance is controver-
sial. 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) kinet-
ics 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 lg⁄mL to
4.87?0.80 lg⁄mL (P<.01) and this increase was
maintained over the next 5 weeks of the HFD
(NE2at week 6 was 4.66?0.97 lg⁄mL). In
addition to the increased NE2there was also a
significant increase in NE clearance (P=.04).
There were significant correlations between the
increase in NE2and 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. J Clin Hypertens
(Greenwich). 2010;12:117–124.ª2009 Wiley
Landsberg and Young1reported that short-term
overfeeding of rats activated the SNS. These and
other observations led Landsberg2to hypothesize
that the increase in SNS activity with weight gain
serves the homeostatic role of stimulating thermo-
genesis to prevent further weight gain. In an
attempt to test this hypothesis there has been con-
siderable controversy regarding the effects of obes-
ity on SNS activation. Data from a review of more
than 40 different studies suggests that whole body
SNS activity, measured by plasma norepinephrine
(NE) concentration, urinary NE excretion, and sys-
temic NE spillover rate into the plasma, is either the
same in lean and obese persons or increases
with increasing obesity.3Masuo and colleagues4,5
reported that plasma NE concentrations not only
increased following weight gain in Japanese men
but plasma NE also appeared to predict subsequent
weight gain and blood pressure (BP) elevation.
he sympathetic nervous system (SNS) plays
an important role in metabolic homeostasis.
From the Department of Pediatrics, Pediatric
Cardiology Division1and the Department of Internal
Medicine, Geriatrics Division,2University of Michigan,
Ann Arbor, MI; and the Department of Internal
Medicine, Geriatrics Division, and Center on Aging,
University of Utah, Salt Lake City, UT;3and the
Department of Veterans Affairs Salt Lake City
Geriatric Research, Education and Clinical Center, Salt
Lake City, UT4
Address for correspondence:
Albert P. Rocchini, MD, University of Michigan
Health System, L1242 Women’s, SPC 5204, 1500 East
Medical Center Drive, Ann Arbor, MI 48109-5204
VOL. 12 NO. 2 FEBRUARY 2010THE JOURNAL OF CLINICAL HYPERTENSION117
In addition, this increase in sympathetic activity
correlates with both the development of insulin
resistance and hypertension.
P2P01HL18575-24, K07 AG028403 and K24 AG00924 from
the National Institutes of Health and the VA Ann Arbor and
Salt Lake City GRECC programs.
was supportedin partby grant
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