Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

R Gosens, D Schaafsma, MMG Bromhaar… - European journal of …, 2004 - Elsevier
R Gosens, D Schaafsma, MMG Bromhaar, B Vrugt, J Zaagsma, H Meurs, SA Nelemans
European journal of pharmacology, 2004Elsevier
Growth factors have been implicated in the pathophysiology of asthma. However, the
putative effects of these growth factors on human airway smooth muscle tone are still largely
unknown. We performed contraction experiments using human bronchial smooth muscle
ring preparations. The growth factor insulin-like growth factor-1 (IGF-1) induced a slowly
developing sustained contraction, which was dependent on Rho-kinase, since contraction
was almost completely inhibited by (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane …
Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor insulin-like growth factor-1 (IGF-1) induced a slowly developing sustained contraction, which was dependent on Rho-kinase, since contraction was almost completely inhibited by (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide (Y-27632; 1 μM). Angiotensin II, a Gq-coupled receptor agonist which can act as a growth factor as well, induced a biphasic contraction, the sustained phase of which was also almost completely inhibited by Y-27632. We conclude that angiotensin II and IGF-1 induce a Rho-kinase-dependent sustained contraction of human bronchial smooth muscle. Since growth factors are associated with pathophysiologiocal conditions such as asthma, inhibition of Rho-kinase could be effective under these conditions.
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