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Rho Kinase inhibitors impair the response of chicken ductus arteriosus to oxygen and other vasoconstrictors
Author(s) -
Villamor Eduardo,
Sterren Saskia,
Agren Pia,
Zoer Bea,
Blanco Carlos E,
Cogolludo Angel L,
PerezVizcaino Francisco
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1239.21
Subject(s) - rho associated protein kinase , phenylephrine , rhoa , contraction (grammar) , rho kinase inhibitor , chemistry , medicine , endocrinology , kinase , signal transduction , biochemistry , blood pressure
Accumulated evidence demonstrates that RhoA/Rho kinase‐mediated increases in calcium sensitivity of the contractile apparatus contributes to ductus arteriosus (DA) contraction. We hypothesized that the contribution of Rho kinase to DA tone is developmentally regulated. In the 19‐day DA (total incubation 21 days), the contractions induced by oxygen, KCl, the inhibitor of K V channels 4‐aminopyridine (4‐AP), the α 1 ‐adrenoceptor agonist phenylephrine, and endothelin‐1 were markedly impaired by the presence of the Rho kinase inhibitors Y‐27632 (10μM) and hydroxyfasudil (10μM). The 15‐d DA did not respond to oxygen or phenylephrine and the response to KCl and 4‐AP was also impaired by Y‐27632 and hydroxyfasudil. During contractions induced by KCl (125 mM), Y‐27632 and hydroxyfasudil (1nM‐10 μM) produced a concentration‐dependent relaxation with a respective ‐log EC50 of 5.7±0.2 and 5.58±0.2 in the 19‐d DA; and 5.0±0.2 and 4.98±0.2 in the 15‐d DA (P<0.05 vs. 19‐d). In conclusion, our data indicate that activation of Rho kinase is a key signalling pathway in oxygen‐, as well as membrane depolarization‐ and receptor stimulation‐induced contraction of chicken embryo DA and that a developmental increase in this pathway occurs during prenatal life. Supported by a grant from “Fundación de Investigación Médica Mutua Madrileña”