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2015 ; 19
(5
): 467-72
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Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood
Pressure Via Inhibition of p66shc Activation
#MMPMID26330760
Kang G
; Lee YR
; Joo HK
; Park MS
; Kim CS
; Choi S
; Jeon BH
Korean J Physiol Pharmacol
2015[Sep]; 19
(5
): 467-72
PMID26330760
show ga
Histone deacetylase (HDAC) has been recognized as a potentially useful
therapeutic target for cardiovascular disorders. However, the effect of the HDAC
inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains
unknown. We performed aortic coarctation at the inter-renal level in rats in
order to create a hypertensive rat model. Hypertension induced by abdominal
aortic coarctation was significantly suppressed by chronic treatment with TSA
(0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven
reactive oxygen species production was also reduced in the aortas of TSA-treated
aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II,
100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded
rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells
(VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation,
which was inhibited by the Ang II receptor type I (AT1R) inhibitor, valsartan (10
µM), but not by the AT2R inhibitor, PD123319. TSA (1~10 µM) inhibited Ang
II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing AT1R.
Taken together, these results suggest that TSA treatment inhibited
vasoconstriction and hypertension via inhibition of Ang II-induced
phosphorylation of p66shc through AT1R.