ABSTRACT
Aim To investigate the vasodilating effect of suberoylanilide hydroxamic acid ( SAHA) on isolated thoracic aorta of rats and the possible mechanisms. Methods Isolated thoracic aorta of rats were used to perfuse, and to observe the effect of accumulated concentration of SAHA (0.3, 1, 3, 10 and 30 p,mol • L_1) on isolated thoracic aorta at basal state, KC1 and NE precontracted state. At the same time, L-NAME, Indo, PMA and SP were used to explore its possible mechanisms of relaxing isolated thoracic aorta, and to investigate the role of the Ca2 during the vasodilating process. Results SAHA could relax KC1 and NE precontracted isolated thoracic aorta of rats (P <0. 01), and the effect on endothelium-intact was stronger than that on endothelium-denuded thoracic aorta (P < 0.01), but there was no significant effect on thoracic aorta at basal state. The vasodilatory effect of SAHA could be inhibited by L-NAME, Indo and PMA (P < 0.05), while that could be promoted by SP ( P < 0. 01). SAHA could attenuate vasoconstriction induced by CaCl2 and NE through inhibiting extracellular Ca2 + influxe and intracellular Ca2 release in a concentration-dependent manner ( P < 0. 01). Conclusions The vasodilating mechanisms of SAHA may be related to the increased production of vasodilatory factors NO and PGt2, and the inhibition of PKC, and the inhibition of extracellular Ca2 + influxe and intracellular Ca2 + release.