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Roles of PKC, RhoA and ERK signaling to serotonergic contractility of pulmonary arteries from chronic hypoxic fetal and adult sheep
Author(s) -
Goyal Ravi,
Mittal Ashwani,
Nguyhn Dan,
Loftin Mathew,
Derrick Allison,
Pearce William J,
Longo Lawrence D,
Wilson Sean M
Publication year - 2009
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.23.1_supplement.619.5
Subject(s) - rhoa , contractility , mapk/erk pathway , endocrinology , protein kinase c , medicine , rho associated protein kinase , kinase , chemistry , signal transduction , biology , microbiology and biotechnology
Serotonin (5‐HT) regulates pulmonary arterial (PA) contractility through Ca 2+ and kinase dependent signaling pathways and many reports indicate these pathways are altered by chronic hypoxia (CH). Among the many kinase pathways activated by 5‐HT, protein kinase C (PKC), Rho kinase, and extracellular regulated kinase (ERK) are important to arterial reactivity. As we have found CH causes selective reductions in Ca 2+ ‐dependent PA contractility in fetus and adult, we used wire‐myography and Western immunoblot techniques to test the hypothesis that CH upregulates kinase‐dependent contractility. PA rings were stimulated with 10 μM 5‐HT and comparative analyses of the kinase pathways were made in the absence and then presence of inhibitors of PKC (1 μM BIM I), RhoA (10 μM Y 27632), and ERK (10 μM U0126). CH did not affect the role for PKC in adult, which did not have an appreciable role in fetus. CH restricted the influence of Rho kinase in fetus and adult, and may cause ERK to become a negative regulator of contractility in adult. CH upregulated ROCK‐II in adult but did not influence the relative expression of PKCα, ERK‐I, ERK‐II, or ROCK‐I in either adult or fetus. In conclusion, maturation and CH cause complex changes in PKC, ERK and Rho kinase‐dependent contractility, which likely integrates with alterations in Ca 2+ ‐signaling to regulate vascular reactivity. Support from NIH, UM, LLUMC, and Sigma Xi.