Journal of Capital Medical University ›› 2013, Vol. 34 ›› Issue (3): 398-403.doi: 10.3969/j.issn.1006-7795.2013.03.015

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DL0805 inhibits the vasoconstriction induced by angiotensin Ⅱ in a Ca2+-dependent and Ca2+-independent manner in the rat aorta

LI Li, YUAN Tianyi, GUO Jing, FANG Lianhua, YANG Haiguang, ZHANG Li, DU Guanhua   

  1. Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
  • Received:2013-04-08 Online:2013-06-21 Published:2013-06-17
  • Supported by:

    This study was supported by the Major Scientific and Technological Special Project for "Significant New Drugs Creation" (2009ZX09302-003, 2013ZX09103001-008), the National Natural Science Foundation of China (81102444, 81102492).

Abstract:

Objective To investigate the mechanisms of DL0805, a Rho kinase inhibitor, in the relaxation on the contraction induced by angiotensin Ⅱ(Ang Ⅱ) in the rat thoracic aorta. Methods Intracellular [Ca2+] ([Ca2+]i) was measured with Fura2/AM in vascular smooth muscle cell(VSMC). Protein level of Rho kinase 1(ROCK1), the phosphorylation levels of myosin phosphatase target subunit 1 (MYPT1) and Akt in the rat aortic rings were detected by Western blotting. Results DL0805 (1, 10 μmol/L) were shown to inhibit both Ang Ⅱ(100 nmol/L)-induced Ca2+ release from internal stores and Ca2+ influx. DL0805 (25、50 μmol/L) significantly attenuated the increased protein level of ROCK1, the increased phosphorylation levels of MYPT1 and Akt in the aorta stimulated by Ang Ⅱ(100 nmol/L). Conclusions DL0805 inhibits the vasoconstriction induced by Ang Ⅱ in a Ca2+-dependent and Ca2+-independent manner in the rat thoracic aorta.

Key words: DL0805, angiotensin Ⅱ, rat thoracic aortic rings, intracellular calcium, Rho kinase, vascular smooth muscle cell

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