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Preventive effect of Clitoria ternatea L. extract on L-NAME-induced left ventricular and vascular dysfunction in rats
ผลป้องกันของสารสกดัดอกอัญชันต่อแอลเนมชักน าให้เกิดการท างานผิดปกติของหัวใจห้องล่างซ้ายและหลอดเลือดในหนูแรท
Male Sprague-Dawley rats were induced hypertension by L-NAME (40 mg/kg) and concomitant with vehicle or CT extract (300 mg/kg) or Lisinopril (2.5 mg/kg) while control group received only distilled water for five weeks. Systolic blood pressure was measured weekly. At the end of experiment, cardiac function, vascular function, oxidative stress markers and NO bioavailability were measured. These findings showed that CT extract and Lisinopril prevents L-NAME-induced hypertension and cardiovascular dysfunction, associated with the reduction of oxidative damage and the improvement of NO bioavailability (p < 0.05).
Hypertension (HT) is an important silent threat, which has many encouraging factors, e.g. oxidative damage and endothelial
dysfunction. HT has been found to impair the function of vital organs, especially heart and blood vessel [1].
Clitoria ternatea L. (CT) known as Anchan in Thai which has been used for food and beverage colorant. CT is rich in anthocyanin and flavonoid glycosides, and it has many biological effects, e.g. anti-inflammation and antioxidation. However, the effects of CT extract in L-NAME-induced hypertensive rats have not been studied yet.
To investigate whether CT extract could prevent L-NAME-induced hypertension and cardiovascular dysfunction in rats
Male Sprague-Dawley rats 200-220 g (n=5)
Distilled water(DW)
L-NAME 40 mg/kg
DW
L-NAME 40 mg/kg
CT 300 mg/kg
L-NAME 40 mg/kg
Lisinopril 2.5 mg/kg
Control L-NAME L+CT L+Lisin
Parameter measurements5 weeks
• Blood pressure: using tail-cuff method
• NO bioavailability- Plasma nitric oxide metabolites (NOx): Enzymatic conversion- eNOS in LV: Western blot analysis
• LV function: Echocardiography
• Vascular function (mesenteric vascular beds):- Relaxation response: perfusion with acetylcholine
• Oxidative stress markers- Superoxide production : Luciginin-enhanced chemiluminescence- Plasma malondialdehyde (MDA): spectrophotometric
0 1 2 3 4 5
0
5 0
1 0 0
1 5 0
2 0 0
2 5 0
C o n t r o l
L -N A M E
L + C T
L + L is i n o p r i l
#
T im e (w e e k s )
Sy
sto
lic
blo
od
pre
ssu
re (
mm
Hg
)*
#
*
*
#
** #
#
*
* #
#
*
#*#
*
* #
#
*$
$$ $$$
**
Parameters Control L-NAME L+CT L+Lisinopril
EDV (ml) 0.74 ± 0.06 0.43 ± 0.09* 0.60 ± 0.11 0.41 ± 0.06*
ESV (ml) 0.17 ± 0.02 0.15 ± 0.03 0.14 ± 0.03 0.08 ± 0.03*
EF (%) 76.74 ± 1.91 69.18 ± 3.12* 76.60 ± 2.00# 81.21 ± 3.41#
SV(ml) 0.57 ± 0.05 0.29 ± 0.06* 0.46 ± 0.08# 0.32 ± 0.04*
FS (%) 40.96 ± 2.23 32.42 ± 2.22* 40.54 ± 1.82# 45.14 ± 3.37#
-8 -7 -6 -5 -4
0
1 0
2 0
3 0
4 0
5 0
L + C T
C o n t r o l
L -N A M E
L + L is i n o p r i l
##
*
A c e ty lc h o lin e [L o g M ]
Dec
rea
se i
n p
erfu
sio
n p
ress
ure
(m
mH
g)
*
**
**
**
#
*
C o n tro l L -N A M E L + C T L + L is in o p r il
0
5 0
1 0 0
1 5 0
2 0 0
2 5 0
C o n tr o l
L -N A M E
L + C T
L + L isin o p r il
#
Su
pe
ro
xid
e p
ro
du
cti
on
(Co
un
t/m
g d
ry
wt/
min
) *
#
#
C o n tro l L -N A M E L + C T L + L is in o p r il
0
3
6
9
1 2
1 5
1 8C o n t r o l
L -N A M E
L + C T
L + L is in o p r i l
#
*
*
Pla
sma
ma
lon
dia
ldeh
yd
e (
M)
#
*
C o n tro l L -N A M E L + C T L + L is in o p r il
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
1 4 0
C o n tr o l
L -N A M E
L + C T
L + L isin o p r il
#
G r o u p s
eN
OS
/-a
cti
n
(% o
f c
on
tro
l)
*
#
C o n tro l L -N A M E L + C T L + L is in o p r il
0
2
4
6
8
1 0
1 2
1 4
C o n t r o l
L -N A M E
L + C T
L + L is i n o p r i l
#
*
G r o u p s
Pla
sma
NO
x (
M)
#
#
*
*
$
ABSTRACT
INTRODUCTION
OBJECTIVES
METHODS
RESULTS
The Effects of CT extract and Lisinopril on;- Figure1: Blood pressure - Figure2: Vasorelaxation response to acetylcholine- Table1 : Cardiac function- Figure3: NO bioavailability; plasma NOx (3A), and eNOS expression in left ventricular (3B)- Figure4: Oxidative stress markers ; vascular superoxide (4A), and plasma MDA (4B)
Data are expressed as mean ± SEM (n = 5-8 / group); * p<0.05 vs. control,
# p<0.05 vs. L-NAME,$ p<0.05 vs. L+CT
Figure 1 Figure 2
Figure 3A Figure 3B
Figure 4A Figure4B
Table 1
PRACTICAL APPLICATION
CONCLUSION
v
CTNO
bioavailability
Oxidative stress
L-NAME rats
Hypertension
Cardiovascular dysfunction
CT extract prevented the development of hypertension and cardiovascular dysfunction induced by L-NAME. It might be associated with the antioxidant effects of CT resulting in improved NO bioavailability.
These findings can be used to study the other effects of CT extract which involve in the antioxidant
property. Moreover, such knowledge is also beneficial to the development of the dietary supplement for hypertension management.
REFERENCE: [1] Konukoglu D, Uzun H. Endothelial Dysfunction and Hypertension. Adv Exp Med Biol2017; 956: 511-540.
METEE IAMPANICHAKUL