Basic & Clinical Medicine ›› 2013, Vol. 33 ›› Issue (6): 699-703.

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ERK1/2 and JNK involved in the inhibitory effect of DL0805 on vasoconstriction induced by angiotensin II in the rat thoracic aortic rings

  

  • Received:2013-02-18 Revised:2013-04-23 Online:2013-06-05 Published:2013-05-29

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

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