6 / 68
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 1, January/February 2015
4
AFRICA
Cardiovascular Topics
In vitro
effects of sodium nitroprusside and leptin on
norepinephrine-induced vasoconstriction in human
internal mammary artery
Oktay Burma, Mete Ozcan, Emine Kacar, Ayhan Uysal, Engin
Ş
ahna, Ahmet Ayar
Abstract
Aim:
The biological and pharmacological properties of
vessels used in coronary artery bypass graft (CABG) surgery
are as important as their mechanical properties. The aim of
this study was to investigate the possible role of protein kinase
C (PKC)-dependent mechanisms in leptin-induced relaxation
in the human internal mammary artery (IMA).
Methods:
IMA rings, obtained from patients undergoing
CABG surgery, were suspended in isolated tissue baths
containing Krebs-Henseleit solution, which were continu-
ously gassed with 95% O
2
and 5% CO
2
at 37°C.
Results:
The IMA rings were pre-contracted with increasing
concentrations of norepinephrine (NE 10
-9
–10
-4
mol/l) and
the relaxation responses to sodium nitroprusside (SNP), a
nitrosovasodilator, and leptin were studied in the presence
and absence of a PKC inhibitor. Leptin (1
μ
M) caused a
dose-dependent relaxation in NE pre-contracted IMA rings.
Pre-treatment with a PKC inhibitor significantly attenuated
this vasorelaxatory response to leptin in human isolated IMA.
Conclusion:
It was found that SNP and leptin caused signifi-
cant relaxation of the NE pre-contracted human IMA rings,
and PKC was probably the sub-cellular mediator for this
effect. Our findings may have clinical or pharmacological
importance as it could be hypothesised that obese subjects
who have a left IMA bypass graft would have better myocar-
dial perfusion.
Keywords:
internal mammary artery, leptin, contraction, protein
kinase C, norepinephrine, sodium nitroprusside
Submitted 3/2/14, accepted 14/7/14
Published online 11/12/14
Cardiovasc J Afr
2015;
26
: 4–7
www.cvja.co.zaDOI: 10.5830/CVJA-2014-041
Coronary heart disease (CHD) and stroke are the largest
contributors to global mortality in low-, middle- and high-
income countries as a result of current lifestyles. They will
continue to cause decreased quality of life and contribute to the
causes of morbidity and mortality throughout the world.
1,2
CHD, also known as coronary artery disease, is the narrowing
of coronary arteries, hampering blood and oxygen supply to
the heart when plaque builds up in the arteries. The heart is an
aerobic organ and disruption of its normal oxygen supply causes
irreversible changes in heart tissue. If the disruption of oxygen
supply is severe, this becomes life threatening.
3
Although CHD cannot be cured, there are several treatment
options to relieve the symptoms and reduce the progression and
risk of complications (heart attack), and thereby prolong the
expected lifespan. Treatment options include lifestyle changes
and medication, but depending on the severity
of the disease,
more aggressive treatment methods including interventional
procedures (angioplasty and stenting) or coronary artery bypass
surgery are warranted.
4
Revascularisation by coronary artery
bypass graft (CABG)
surgery is a process of restoring the blood flow around existing
blockages to the heart using autologous bypass grafts (or artificial
grafts). The immediate success of this procedure is related to
surgical technique and the anatomical characteristics of the
grafted coronary artery.
5
After grafting, the vascular smooth
muscle cells of the new vessels are the primary regulators of
vascular tone. Therefore characterisation of the contractile and
relaxatory profiles of the commonly used graft vessels in response
to major coronary vasodiladator and vasoconstrictor agents has
been carried out in
in vitro
pharmacological investigations.
The effects of noradrenaline, dopamine,
6
adenosine and nitric
oxide
7,8
are well established, but other endogenous agents
9
that
increase in concentration in the circulation during cardiovascular
disease are poorly studied. Leptin is a hormone secreted mostly
from adipocytes, which is also produced in small amounts from
Department of Cardiovascular Surgery, Faculty of
Medicine, Firat University, Elazig, Turkey
Oktay Burma, MD,
oburma@firat.edu.trAyhan Uysal, PhD
Department of Biophysics, Faculty of Medicine, Firat
University, Elazig, Turkey
Mete Ozcan, PhD
Department of Physiology, Faculty of Medicine, Firat
University, Elazig, Turkey
Emine Kacar, MD
Department of Pharmacology, Faculty of Medicine, Firat
University, Elazig, Turkey
Engin
Ş
ahna, PhD
Department of Physiology, Faculty of Medicine, Karadeniz
Technical University, Trabzon, Turkey
Ahmet Ayar, PhD