CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 2, March 2012
98
AFRICA
Experimental malaria: the
in vitro
and
in vivo
blood
pressure paradox
CR NWOKOCHA, MI NWOKOCHA, DU OWU, IO AJAYI, AB EBEIGBE
Abstract
Objective:
Malaria causes more deaths worldwide than any
other parasitic disease. Many aspects of the biology that
governs the pathogenesis of this parasite are still unclear.
Therefore insight into the complexity of the pathogenesis of
malaria is vital to understand the disease, particularly as it
relates to blood pressure.
Methods:
In vivo
and
in vitro
experimental models were used
for this study. In the
in vivo
study, mean arterial pressure,
pulse rates and heart rates were recorded by cannulation of
the carotid artery of rats. In the
in vitro
study, ring prepara-
tions of blood vessels from the rat aorta were studied using
standard organ bath techniques. Dose–response curves for
phenylepherine (PE)- and acetylcholine (Ach)-induced relax-
ation were constructed for rings pre-contracted with PE.
Results:
Our results showed a significant (
p
<
0.05) reduction
in the mean arterial pressure and pulse rates, while the heart
rates remained unaltered in rats with malaria parasites,
compared with the controls. Incubation of rat aortic rings
with parasitised blood resulted in a significant (
p
<
0.05)
increase in maximum contractile response to phenylephrine
in the rat aortic rings but there was no effect on the baseline.
The dose–response curve showed a significant (
p
<
0.05)
leftward shift following the addition of parasitised blood and
the EC
70
(M) values increased from 7
×
10
-7
to 5
×
10
-6
M.
Following exposure to parasitised blood, the magnitude of
Ach-induced relaxation responses reduced significantly (
p
<
0.05) from 73
±
3.6 to 24.75
±
7.25% in the rat aortic rings.
Conclusions:
The results suggest that malaria parasitaemia
caused
in vivo
reduction in blood pressure, and enhanced
the responses to contractile agents and reduced relaxation
responses to acetylcholine
in vitro
. This appears to be a para-
dox but is explainable by the complex cardiovascular control
mechanisms
in vivo
. This may be independent of direct action
on vascular smooth muscle.
Keywords:
blood pressure, blood vessel, malaria, vascular reac-
tivity
Submitted 27/9/10, accepted 21/9/11
Cardiovasc J Afr
2012;
23
: 98–102
DOI: 10.5830/CVJA-2011-059
Malaria causes more deaths worldwide than any other parasitic
disease and it is responsible for an estimated 1.5 to 2.7 million
deaths annually.
1
Many aspects of the molecular biology, immu-
nology and epidemiology that govern the pathogenesis of this
parasite are still unclear and such insight into the complexity of
malarial pathogenesis is vital to understand the disease.
The capacity of
Plasmodium falciparum
to cause severe
and fatal disease is believed to be in part due to its ability to
sequester in post-capillary venules. Severe
falciparum
malaria is
associated with tissue ischaemia related to the cyto-adherence of
parasitised erythrocytes to the microvascular endothelium, and
reduced levels of nitric oxide (NO) and its precursor, L-arginine.
2
Malaria has been reported to produce alterations in cardiovascu-
lar function.
3,4
Reports in the literature are conflicting; whereas some work-
ers reported a fall in blood pressure (BP) in
falciparum
malaria,
5-8
others have associated it with hypertension and severe intracra-
nial hypertension.
9,10
An increase in cardiac output and systolic
right ventricular pressure but reduced heart rate, total peripheral
vascular resistance and mean arterial blood pressure have been
reported with rising parasitaemia.
3
Malaria is associated with
significant lengthening of the QT interval, which could predis-
pose to potentially lethal polymorphic malignant ventricular
tachyarrhythmias.
11,12
The release of haemoglobin (Hb) through intravascular
haemolysis, which is then able to scavenge endothelium-derived
NO 600-fold faster than erythrocytic haemoglobin, is a central
pathophysiological event leading to vascular complications,
13-19
and may contribute to pulmonary arterial hypertension, periph-
eral vasculopathy and stroke. This is because NO plays a major
role in vascular homeostasis and has been shown to be a critical
regulator of basal and stress-mediated smooth muscle relaxa-
tion, vasomotor tone, endothelial adhesion molecule expression,
platelet activation and aggregation.
13-15
Parasitised red cells adhere to constitutive and cytokine-
inducible receptors on the microvascular endothelium, result-
ing in sequestration, vascular obstruction, impaired perfusion,
endothelial inflammation and damage.
20-24
They also contribute
to the synthesis and release of cytokines and even neurotransmit-
ters,
21-23
the impaired cerebral synthesis of serotonin, dopamine,
histamine and norepinephrine,
24,25
and endothelial cell activa-
tion.
26
All these further compound the situation, leading to local
metabolic derangements.
5,26,27
With increasing sensitivity to vasoconstrictors, vascular
resistance is expected to increase, leading to an elevation in
blood pressure. The role of cardiac dysfunction in the pathogen-
esis of severe malaria remains unknown or relatively confusing.
The aim of this study was to evaluate, using
in vitro
and
in vivo
Department of Basic Medical Sciences, University of the
West Indies, Kingston, Jamaica
CR NWOKOCHA, MB BS,
DU OWU, PhD
Department of Physiology, University of Benin, Benin City,
Nigeria
IO AJAYI, PhD
AB EBEIGBE, PhD
Kingston Public Hospital, Kingston Jamaica
MI NWOKOCHA, PhD
