Abstract: Objective To observe the effect of DL0805 (a Rho kinase inhibitor) on angiotensin II (Ang Ⅱ) -induced vascular contractions in the rat thoracic aortic rings and to investigate the possible mechanism. Methods The isometric vascular tone was measured in both endothelium-intact and endothelium-denuded rat thoracic aortic rings. Phosphorylations of p44/42 extracellular signal-regulated kinase (ERK1/2) and c-Jun amino-terminal kinase (JNK), and protein level of angiotensin type 1 receptor (AT1R) in rat aortic rings were detected by Western blot. Results DL0805 (10、25 and 50 μmol/L) inhibited Ang Ⅱ（100 nmol/L）-induced vascular contractions in both endothelium-intact and endothelium-denuded rat aortic rings in a dose dependent way （P < 0.01, P < 0.001）. Furthermore, activation of ERK1/2 and JNK by Ang Ⅱ（100 nmol/L）stimulation was significantly inhibited by DL0805 (25 and 50 μmol/L) in both endothelium-intact and -denuded rat aortic rings （P < 0.05, P < 0.01 and P < 0.001）. However, the protein level of AT1R in response to Ang Ⅱ was not affected by DL0805 (5、25 and 50 μmol/L) in rat aortic rings. Conclusion DL0805 inhibits Ang Ⅱ-induced rat aortic rings contraction and the mechanism involves the inhibition of Ang II-induced ERK1/2 and JNK activation.

Key words: DL0805, angiotensin II, rat thoracic aortic rings, ERK1/2, JNK