CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 2, March 2012
100
AFRICA
5
×
10
-6
M for the tissues exposed to parasitised blood.
Incubation with parasitised blood alone did not affect the resting
tension in the rings studied, and did not cause the relaxation of
the phenylephrine pre-contracted rings when added to the organ
baths (not shown).
Endothelium-dependent acetylcholine-induced relaxation
responses were examined in the phenylephrine (10
-7
M) pre-
contracted rings. Parasitaemia significantly (
p
<
0.05) attenuated
acetylcholine-induced relaxation of the aortic rings following
exposure to parasitised blood (Fig. 5).
Discussion
In the
in vivo
studies, we observed that the mean arterial pres-
sure and pulse rates were significantly reduced in the parasitised
animals, while the heart rates were not altered. This is partly in
agreement with Shida,
3
who reported a reduced mean arterial
blood pressure and heart rate.
There was no decrease in heart rates in our parasitised group,
compared with the controls and hence the hypotension observed
cannot be attributed to bradycardia. The hypotension can also not
be explained as an autonomic (sympathetic) activity as there was
also a reduction in the pulse rates. This decrease in blood pres-
sure could have been associated with impaired cerebral synthesis
of serotonin, dopamine and norepinephrine, enhanced produc-
tion of histamine,
24, 25
and reduced levels of NO and its precursor,
l-arginine, which may lead to vasodilation
in vivo
.
In the
Plasmodium berghei
ANKA (PbA) murine model of
Cabrales
et al
., cerebral malaria pathogenesis was associated
with low nitric oxide (NO) bioavailability and brain microcircu-
latory complications, with a marked decrease in cerebral blood
flow, vasoconstriction, vascular plugging by adherent cells, and
haemorrhage.
33
The tone of blood vessels is determined by their responsive-
ness to contracting agonists. In the present study, incubation with
parasitised blood resulted in a significant increase in maximum
contractile response to phenylephrine in the rat aortic rings.
Analysis of the whole dose–response curve showed a significant
leftward shift of the curve following the addition of parasitised
blood. There was increased sensitivity to phenylephrine in the
aortic rings exposed to parasitised blood. We also observed a
significant reduction in the magnitude of Ach-induced relaxation
following exposure to parasitised blood.
Shida
et al
.
3
had earlier reported a decline in the total periph-
eral vascular resistance, but our observations were an enhanced
vascular reactivity
in vitro
. This increased vascular reactivity
could lead to elevated blood pressure. The enhanced contractions
with parasitised blood could have been due to the non-specific
immune inflammatory response of the host to the malaria para-
site, with the release of various mediators into the blood stream,
and local synthesis of cytokines or even neurotransmitters
21-23
associated with endothelial inflammation and damage.
34-36
Previous studies have reported an overall reduction in nitric
oxide availability with malaria infection.
14-16
Increased cell-
free haemoglobin and plasma arginase
13,15-19
would have caused
reduced nitric oxide availability, which could possibly have
affected the relaxation responses to acetylcholine and also
enhanced the phenylephrine-induced contraction.
The enhanced production of histamine and NO
24
would be
expected to cause vasodilation, while local cytokine produc-
tion
25
would be expected to cause an increase in vascular tone.
Incubation of the aorta with malaria-parasitised blood did not
have any effect on baseline contractions. This suggests that inter-
action between malaria parasites and the blood vessel wall (
in
vitro
) resulted in functional changes in the contractile state of the
vascular smooth muscles, possibly through the release of vaso-
active agents from both the red cells and vascular endothelium.
37
With malaria infection, the vasculature exhibits not only an
impaired vasorelaxant response but also a markedly exagger-
ated vasoconstrictive response. This enhanced sensitivity of the
Fig. 3. Heart rate in control and malaria-parasitised rats.
160
120
80
40
0
Heart rate (beats/min)
control
malaria group
Fig 4. Influence of parasitaemia on phenylephrine concen-
tration response curves in aortic rings. Data are means
±
SE (
n
=
6)
Phenylephrine (Log M)
100
80
60
40
20
0
% Contraction
control
parasitized blood
–9
–8
–7
–6
–5
–4
Fig. 5. Ach-induced relaxations of aorta following expo-
sure to parasitised blood. Data are means
±
SE of tissues
(
n
=
6)
Acetylcholine (Log M)
0
20
40
60
80
% Relaxation
control
parasitised blood
–10
–8
–6
–4
