1. 1Anthony Eller; 2Nancy Smith-Blair PhD
1Department of Chemistry and Biochemistry, 2Department of Nursing
University of Arkansas
INTRODUCTION
METHODS AND MATERIALS
Timeline
REFERENCES
Figure 2. Two male Zucker rats. Figure 3. Dissected rat.
ABSTRACT
CONTACT
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Anthony Eller
Email:
ajeller@email.uark.edu
Phone: (816) 809-9264
Current research indicates
that uncontrolled diabetes
is associated with the
development of pulmonary
artery hypertension (PAH)
independent of coronary
artery disease,
hypertension, congestive
heart failure, or smoking,
however the underlying
mechanism behind the
incidence is not fully
understood. The purpose
of this study is to explore
the mechanism behind
pulmonary artery
contraction in pulmonary
artery hypertensive (PAH)
patients with diabetes
mellitus type II.
 Diabetes mellitus type II (DMII) is among the 10
leading causes of death in Arkansas and
nationwide as the rates continue to climb; 17.9
million were diagnosed in 2010 (Biddle, 2011)
 Uncontrolled diabetes contributes to the
development of PAH
 Impaired endothelial function is common among
patients with diabetes and animal studies have
indicated impaired acetylcholine-medicated
relaxation of the aorta and other systemic
vascular rings though it is unclear the effect on
pulmonary artery rings (Biddle, 2011)
 PAH ultimately results in right sided heart failure
because of the decrease in synthesis of
endothelium-derived vasodilators such as nitric
oxide resulting in constant contraction
(Iannaccone, 2009)
 iNOS inhibitor L-NAME is suspected to increase
NO synthesis, thus increasing vasodilation
 This study will examine the vasoconstrictor
response of obese Zucker rats, in which PAH has
been induced, to the iNOS inhibitor L-NAME
1. Biddle, J. (2011). The burden of diabetes in
Arkansas. Arkansas Department of Health
2. Iannaccone PM, Jacob HJ. (2009). Rats! Dis
model Mech: 206-210.
3. Miller, M., Thompson, J., & Liu, X. (1996).
Failure of l-name to cause inhibition of nitric
oxide synthesis: role of inducible nitric oxide
synthase. Inflammation Research, 45(6), 272-.
August 2014 Receive animals and induce PH
in one group and be trained in
laboratory techniques
necessary to conduct
experiments
September 2014 Weigh animals daily and check
blood glucoses weekly;
continue training in laboratory
techniques
October and November 2014 Terminal laboratory
experiments
December 2014 Analyze data and report
findings
 Ten male Zucker rats 4 weeks of age approximately
100-150 gms will be used
 For 28 days they will be allowed food (Gloval diet
20-18 F non-sterile diet) and water while being
placed on a reversed 12:12 light-dark cycle.
Environmental conditions will be maintained at
approximately 50% relative humidity around 72o F
 CLAF standard cage bedding for rodents will be
used and will be routinely changed
 Body weights will be measured daily along with
weekly testing of blood glucose obtained via tail
using an Accu-Check Active meter
 Following 28 days of sedentary activity, rats will be
euthanized with pentobarbital 150 mg/kg IP then
the pulmonary artery will be dissected
 Pulmonary artery rings 2-3 mm long will be
dissected with an internal diabeter and mounted in
Schuler tissue bath in Krebs solution at 37o C
gassed with 95%O2-5%CO2 mixture
 Resting tension will be at 0.75 g and rings will be
pre-contracted with 1-µmol phenylephrine and a
concentration-response curve to acetylcholine (1-
µmol) performed by cumulative addition
 Tissue will be washed and allowed to equilibrate to
the resting tension then rings will again be
contracted with 1-µmol phenylephrine,
acetylcholine 1-µmol will be added along with 1-
µmol L-NAME
 Resting tension and peak force contraction will be
measured by a force and displacement transducer
Research Questions
1. Is there a difference be contractile properties
between obese Zucker rats and PAH induced
obese Zucker rats in the presence of iNOS
inhibitor L-NAME?
2. Is there a difference in relaxant properties
between obese Zucker rats and PAH induced
obese Zucker rats in the presence of iNOS
inhibitor L-NAME?
Figure 1. Molecular pathway of vasodilation
mediated by NO and cGMP