Pflügers Archiv - European Journal of Physiology

, Volume 460, Issue 3, pp 645–655

Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats

  • Hiroyasu Sakai
  • Yuko Nishizawa
  • Ayako Nishimura
  • Yoshihiko Chiba
  • Kumiko Goto
  • Motohiko Hanazaki
  • Miwa Misawa
Muscle physiology

DOI: 10.1007/s00424-010-0844-y

Cite this article as:
Sakai, H., Nishizawa, Y., Nishimura, A. et al. Pflugers Arch - Eur J Physiol (2010) 460: 645. doi:10.1007/s00424-010-0844-y

Abstract

Angiotensin II (Ang II) might be an important mediator in the pathogenesis of bronchial asthma, although the mechanisms of airway hyperresponsiveness caused by Ang II are not yet clear. Whether p42/44 ERK contributes to the Ang II-elicited bronchial smooth muscle (BSM) hyperresponsiveness in rats was presently examined. The RT-PCR analyses revealed that Ang II AT1A, AT1B, and AT2 receptors, angiotensinogen, angiotensin-converting enzyme, but not renin, were expressed in the lungs, trachea, and main bronchi of rats. Only a small and transient contraction was induced by the application of Ang II in the main bronchial smooth muscle; the contraction was inhibited by losartan, an AT1 receptor antagonist. The contractions induced by carbachol (CCh), high K+ depolarization, and sodium fluoride (NaF; a G protein activator) were augmented by pretreatment with Ang II. The BSM hyperresponsiveness induced by Ang II was abolished by losartan. Furthermore, the Ang II-induced BSM hyperresponsiveness to CCh was attenuated by pretreatment with U-0126, a p42/44 ERK kinase (MEK-1/2) inhibitor. In conclusion, Ang II-induced BSM hyperresponsiveness through the activation of p42/44 ERK may play an important role in the pathophysiology of bronchial asthma, although Ang II itself caused a small force development in the bronchial smooth muscle.

Keywords

Airway hyperresponsivenessAngiotensin IIp42/44 ERKBronchial smooth muscle

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hiroyasu Sakai
    • 1
  • Yuko Nishizawa
    • 1
  • Ayako Nishimura
    • 1
  • Yoshihiko Chiba
    • 1
  • Kumiko Goto
    • 1
  • Motohiko Hanazaki
    • 1
  • Miwa Misawa
    • 1
  1. 1.Department of Pharmacology, School of PharmacyHoshi UniversityShinagawa-kuJapan