Angiotensin II induces hyperresponsiveness of bronchial smooth muscle via an activation of p42/44 ERK in rats.
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.
Sakai
Hiroyasu
H
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan. sakai@hoshi.ac.jp
Nishizawa
Yuko
Y
Nishimura
Ayako
A
Chiba
Yoshihiko
Y
Goto
Kumiko
K
Hanazaki
Motohiko
M
Misawa
Miwa
M
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
D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases