Proceedings of the British Pharm
macological Sociiety at http://www
w.pA2online.org/a
/abstracts/Vol13Isssue3abst047P.p
pdf
sin 1-7prottects again
nst angiote
ensin II-ind
duced endo
oplasmic reticulum
r
Angiotens
stress and
d endothellial dysfunction via M
Mas recepttor
ardiovascular actions of an
ngiotensin II (A
Ang II) (1). The
Angiotensin 1-7 (Ang 1-7) counter-regulates the ca
d the protectiive effect of A
Ang 1-7 again
nst Ang II-induced endopla
asmic reticulu
um
present study investigated
elial dysfuncttion. Vascular reactivity in
n mouse aorrtae was eva
aluated by wire
(ER) stress and endothe
he effects off Ang 1-7 on
o Ang II-ind
duced ER sttress markerrs, nitric oxid
de activity and
myograph.Th
generation in
i the mous
se aortas an
nd HUVECs were assesssed by we
estern blot and
a
4-amino--5methylamino
o-2',7'-difluoro
ofluorescein (DAF-DA,
(
1 μ
μM), respectively. Ex vivo
o treatment with
w Ang II (0
0.5
µM, 24 hourrs) impaired endothelium-d
e
dependent relaxation in mouse aortas; this harmful effect of Ang
g II
was revers
sed byco-tre
eatment with
h ER stress inhibitorss, l4-phenyllbutyric acid
d (PBA) and
tauroursodeo
oxycholic acid (TUDCA) as
a well as A
Ang 1-7 (Fig 1). The Mass receptor an
ntagonist, A779
antagonized the effect of Ang 1-7. The
e elevated mR
RNA expression of CHOP,, Grp78 and ATF4
A
or prote
ein
expression of
o p-EIF2α and ATF6 (ER stress
s
markerrs) in Ang II-treated mouse
e aortas were
e blunted by coc
treatment with Ang 1-7 and the latter effect was re
eversed by A7
779 (Fig 2). Furthermore,
F
Ang II-induced
on and NO prroduction was
s inhibited byy Ang 1-7.The
e present study
reduction in botheNOS phosphorylatio
provides new
w evidence fo
or functional antagonism
a
b
between the two arms of th
he renin-angiiotensin syste
em
in endothelia
al cells by de
emonstrating that
t
Ang 1-7 ameliorates Ang II-stimullated ER stre
ess to raise NO
N
bioavailability
y, and subseq
quently prese
erves endothe
elial function.
C
Fig 1. ER stress
s
inhibittors (A and B)
B and Ang 1-7
1 (C) revers
sed Ang IIinduced im
mpaired of Ach-induced rrelaxation
Fig 2. Ang
A 1-7 decre
eased Ang II stimulated ER
E stress
Reference:
(1) Galaan et al., (2014). Biochim. BiophysActa
B
1843: 1063-7
75