title: Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats.
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 AT(1A), AT(1B), and AT(2) 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 AT(1) 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. sakai@hoshi.ac.jp
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Nishimura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Chiba
authors.forename: Kumiko
authors.initials: K
authors.lastname: Goto
authors.forename: Motohiko
authors.initials: M
authors.lastname: Hanazaki
authors.forename: Miwa
authors.initials: M
authors.lastname: Misawa
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism* / Q000503:physiopathology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression; D009130:Muscle, Smooth / Q000503:physiopathology*; D051381:Rats; D012084:Renin-Angiotensin System
chemical_list: D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases