CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 3, May/June 2010
Cardiovascular Topics
132
AFRICA
Dual effect of quercetin on rat isolated portal vein
smooth muscle contractility
WITNESS DH CHIWORORO, JOHN AO OJEWOLE
Summary
This study examined the effects of quercetin on spontaneous-
ly contracting portal veins isolated from healthy young adult
male and femaleWistar rats (250–300 g). Quercetin (10
-7
–10
-4
M) always produced significant biphasic effects, comprising
an initial brief stimulant effect (rise in basal tone), followed
by a sustained, longer-lasting secondary relaxant (inhibitory)
effect on the venous tissues. The initial brief contractions of
the venous muscle preparations were not modified by pre-
incubation of the tissues with prazosin (10
-6
M), suggesting
that the initial upsurge in basal tone and increases in contrac-
tile frequencies of the venous tissues were probably not
mediated via alpha
1
-adrenoceptor stimulation. However, pre-
incubation of the tissues with nifedipine (10
-7
M) significantly
suppressed (
p
<
0.05) or attenuated the initial stimulant effect
of quercetin, suggesting that the flavonoid might be activat-
ing L-type voltage-dependent calcium channels. The vasore-
laxant effect of quercetin was partially but not significantly
(
p
>
0.05) inhibited by L-NAME (100
µ
M) or indomethacin
(10
µ
M), suggesting that the vasorelaxant effect of the flavo-
noid was unlikely to be mediated via endothelium-dependent
relaxing factor (EDRF), or through prostacyclin (PGI
2
) path-
ways.N-p-tosyl-l-phenylalanine-chloromethyl-ketone (TPCK,
3
µ
M) significantly (
p
<
0.01) antagonised quercetin-induced
relaxations, suggesting that cAMP-dependent protein kinas-
es might have contributed, at least in part, towards the
vasorelaxant effect of quercetin on rat isolated portal veins.
Keywords:
rat isolated portal vein, quercetin, dual effects,
endothelium-dependent relaxing factor, prostacyclin, cAMP-
dependent protein kinases
Submitted 7/3/09, accepted 14/8/09
Cardiovasc J Afr
2010;
21
: 132–136
Quercetin is a naturally occurring polyphenolic bioflavonoid that
is widely distributed throughout the plant kingdom, including
edible plants, mainly onions, apples, grapes, guavas, avocados,
herbs, spices, berries and grains, and beverages, mostly teas and
red wines.
1
Several epidemiological studies have revealed that
the Mediterranean diet, based primarily on dietary flavonoids
(mainly quercetin) correlates with increased longevity,
2
and
decreased incidence of cardiovascular diseases.
3-6
Quercetin has been shown to possess a wide spectrum of
physiological and pharmacological properties responsible for its
beneficial effects on the cardiovascular system.
7
In fact, quecetin
modifies eicosanoid biosynthesis, resulting in antiprostanoid and
anti-inflammatory responses; protects low-density lipoprotein
from oxidation, thus preventing atherosclerotic plaque forma-
tion; and prevents platelet aggregation and promotes relaxation
of vascular smooth muscles.
1,8
Studies by Duarte and co-workers
have shown that quercetin possessed antihypertensive effects
and lowered left ventricular hypertrophy, endothelial dysfunc-
tion and plasma and hepatic oxidative status in spontaneously
hypertensive rats.
9,10
The pharmacological effects of flavonoids on plasma
membrane ion transport proteins such as Ca
2+
-Mg
2+
-ATPase,
Na
+
-K
+
-ATPase and mitochondrial ATPase, as well as inhibi-
tion of cAMP- or cGMP-phosphodiesterase and protein kinases
have been described.
11-15
Moreover, the possible involvement of
quercetin on L-type calcium channels has been reported.
1,16
The
possible involvement of myosin light-chain kinase in flavonoid-
induced smooth muscle relaxation has also been raised.
17-19
Quercetin has been reported to inhibit Ca
2+
-sensitising mecha-
nisms in contractile proteins such as protein kinase C.
7
Other
earlier investigators have postulated a different mechanism
which involves intracellular cAMP increase
11-14
due to inhibition
of cAMP-phosphodiesterase (PDE).
20-22
Earlier studies have shown that quercetin and its metabolites
(isorhamnetin, tamarixetin and kaempferol) exhibited vasodilato-
ry effects on rat isolated aortic ring preparations.
18,23,24
Generally,
flavonoids have been postulated to evoke their vasodilatory
effects through the release of endothelium-derived relaxing
factors such as nitric oxide (NO) and prostacyclin (PGI
2
).
18,25
However, there have been conflicting reports about the role of
endothelium in the flavonoids’ vasorelaxant effects. Indeed, the
vasorelaxant effects of several groups of flavonoids have been
demonstrated to be endothelium dependent
25
or endothelium
independent.
26,27
An extensive literature search has failed to reveal any study
dealing with the effects of quercetin on portal vein preparations.
The present study, therefore, examined the effects of quercetin
on rat isolated portal veins, and attempted to characterise the
possible underlying mechanisms involved in quercetin-induced
vasorelaxation.
Methods
Experimental protocols and procedures used in this study were
approved by the Animal Ethics Committee of the University of
Department of Pharmacology, University of KwaZulu-Natal,
Durban, South Africa
WITNESS DH CHIWORORO, BPharm, MSc (Pharmacol)
JOHN AO OJEWOLE, BPharm (Hons), MSc (Clin Pharm), PhD
(Pharmacol),
