Limits...
Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation.

Kang G, Lee YR, Joo HK, Park MS, Kim CS, Choi S, Jeon BH - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Trichostatin A (TSA) inhibited angiotensin II (Ang II)-induced vasoconstriction in rat aorta. Vasoconstriction was evoked by Ang II treatment at doses between 1 and 100 nM in aortic rings with intact (A) or rubbed endothelium (B). Contraction was expressed as a percentage of the pre-contracted tension obtained with a high K+ (60 mM) solution. Each bar represents the mean±S.E.M. (n=6). Control: DMSO vehicle. *p<0.05 (vs. control), **p< 0.01 (vs. control).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4553407&req=5

Figure 2: Trichostatin A (TSA) inhibited angiotensin II (Ang II)-induced vasoconstriction in rat aorta. Vasoconstriction was evoked by Ang II treatment at doses between 1 and 100 nM in aortic rings with intact (A) or rubbed endothelium (B). Contraction was expressed as a percentage of the pre-contracted tension obtained with a high K+ (60 mM) solution. Each bar represents the mean±S.E.M. (n=6). Control: DMSO vehicle. *p<0.05 (vs. control), **p< 0.01 (vs. control).

Mentions: We investigated whether TSA influences Ang II-induced vasoconstriction in rat aortas. Aortic rings were pretreated with TSA (1~10 µM) for 15 min. As shown in Fig. 2A, TSA pretreatment inhibited Ang II-induced vasoconstriction in endothelium-intact aortic rings. The inhibitory activity of TSA on Ang II-induced vasoconstriction showed a dose dependency. Interestingly, TSA also inhibited Ang II-induced vasoconstriction in endothelium-rubbed aortic rings (Fig. 2B). The inhibitory action of TSA in endothelium-rubbed aortic rings was much greater than that for the intact endothelium, suggesting that TSA has mainly acted in VSMCs.


Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation.

Kang G, Lee YR, Joo HK, Park MS, Kim CS, Choi S, Jeon BH - Korean J. Physiol. Pharmacol. (2015)

Trichostatin A (TSA) inhibited angiotensin II (Ang II)-induced vasoconstriction in rat aorta. Vasoconstriction was evoked by Ang II treatment at doses between 1 and 100 nM in aortic rings with intact (A) or rubbed endothelium (B). Contraction was expressed as a percentage of the pre-contracted tension obtained with a high K+ (60 mM) solution. Each bar represents the mean±S.E.M. (n=6). Control: DMSO vehicle. *p<0.05 (vs. control), **p< 0.01 (vs. control).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553407&req=5

Figure 2: Trichostatin A (TSA) inhibited angiotensin II (Ang II)-induced vasoconstriction in rat aorta. Vasoconstriction was evoked by Ang II treatment at doses between 1 and 100 nM in aortic rings with intact (A) or rubbed endothelium (B). Contraction was expressed as a percentage of the pre-contracted tension obtained with a high K+ (60 mM) solution. Each bar represents the mean±S.E.M. (n=6). Control: DMSO vehicle. *p<0.05 (vs. control), **p< 0.01 (vs. control).
Mentions: We investigated whether TSA influences Ang II-induced vasoconstriction in rat aortas. Aortic rings were pretreated with TSA (1~10 µM) for 15 min. As shown in Fig. 2A, TSA pretreatment inhibited Ang II-induced vasoconstriction in endothelium-intact aortic rings. The inhibitory activity of TSA on Ang II-induced vasoconstriction showed a dose dependency. Interestingly, TSA also inhibited Ang II-induced vasoconstriction in endothelium-rubbed aortic rings (Fig. 2B). The inhibitory action of TSA in endothelium-rubbed aortic rings was much greater than that for the intact endothelium, suggesting that TSA has mainly acted in VSMCs.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747, Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus