PS 07-29 FLAVONE DERIVATIVE, CSH-3-124 DECREASES ARTERIAL BLOOD PRESSURE THROUGH INHIBITION OF ANGIOTENSIN II

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Abstract

Objective:

Flavones are polyphenolic compounds that are included in the human diet such as vegetables and nuts. A number of studies have suggested that higher flavonoid intake is associated with lower cardiovascular mortality. This study was designed to investigate the inhibitory effects of a novel flavonoid derivative, CSH-3-124; (E)-2-(3,4-dimethoxyphenyl)-4-oxo-4H-chromen-7-yl 3-(pyridine-3-yl)acylate, on angiotensin II(Ang II) and to examine the vasodilator effects of it.

Objective:

Design and Method: To investigate the effects of flavone derivative, CSH-3-124 on Ang II, the vascular smooth muscle cells(VSMCs) proliferation and migration assay was done. Primary cultured VSMCs from male Sprague-Dawley rat aorta were stimulated by Ang II and examined with or without CSH-3-124. To evaluate the vasodilator effects, the isometric tension of rat thoracic aorta was recorded by using multi-wire myograph systems with or without CSH-3-124. In vivo, blood pressure(BP) was measured with or without intraperitoneal injection of CSH-3-124 after Ang II infusion with mini-osmotic pump in C57B6 mice.

Results:

The proliferation and migration of VSMCs by Ang II was inhibited significantly when added Ang II and CSH-3-124 together compared to Ang II only (control; 1.00 ± 0.03/1.00 ± 0.18 folds vs. Ang II; 1.71 ± 0.14/0.37 ± 0.07 folds vs. Ang II and CSH-3-124; 0.87 ± 0.05/0.83 ± 0.09 folds as relative cell counting for proliferation/relative wound area for migration, p < 0.05). The CSH-3-124 showed a dose dependent vasorelaxation (96.5% for 10−6 M, 72.1% for 10−5 M, 37.8% for 10−4 M as percent of vasocontracting effect of phenylephrine 10−7 M). The Ang II-induced hypertension in mice was decreased after CSH-3-124 treatment (0.75 ± 22.69 for control vs. −66.53 ± 4.44 and −67.88 ± 2.68 mmHg for CSH-3-124 10−4M and 10−5 M as a change of BP after 3 hours, p < 0.05).

Conclusions:

In conclusion, a flavone derivative, CSH-3-124 inhibited the VSMCs proliferation and migration, and decreased blood pressure through suppression of Ang II. We suggest that CSH-3-124 can be a useful treatment for cardiovascular disease including hypertension.

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