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Rho/rho‐kinase pathway is up‐regulated in pulmonary vessels of pregnant ewes in chronic high altitude hypoxia
Author(s) -
Chai Edward Ekmaha,
Negash Sewite,
Gao Yuansheng,
Raj J Usha,
Longo Lawrence D.
Publication year - 2007
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.21.5.a406-c
Subject(s) - rho associated protein kinase , protein kinase a , cgmp dependent protein kinase , hypoxia (environmental) , endocrinology , medicine , nitric oxide , hypoxic pulmonary vasoconstriction , kinase , chemistry , signal transduction , pulmonary hypertension , biology , biochemistry , cyclin dependent kinase 2 , oxygen , organic chemistry
Chronic hypoxia induces pulmonary hypertension and abnormal vascular reactivity. In this study, we examined the effect of chronic high altitude hypoxia (HAH) on relaxation responses of pulmonary arteries (PA) and veins (PV). Isolated intrapulmonary PA and PV from pregnant ewes exposed to HAH for 110 d or matched sea level controls were preconstricted with endothelin‐1 and relaxed to 8‐bromoguanosine 3′,5′‐cyclic monophosphate (8‐Br‐cGMP). Roles of cGMP‐dependent protein kinase (PKG) and Rho‐kinase (ROCK) were assessed by determining cGMP‐mediated relaxation in the presence of Rp‐8‐Br‐cGMPS (PKG inhibitor) and Y27632 (Rho‐kinase‐specific inhibitor). ROCK protein expression and activity were measured. We found that relaxation to cGMP was decreased in HAH PV compared to controls. Inhibition of PKG did not affect cGMP‐mediated relaxation in either control or HAH PV. Inhibition of ROCK with Y27632 restored relaxation to cGMP in HAH PV to comparable levels as in control PV, suggesting increased Rho/ROCK signaling in chronic HAH. Western blot analysis showed increased protein expression of ROCK‐1 and ROCK‐2, and increased expression of phosphorylated MYPT‐1 serine 696 and threonine 853, indicating increased ROCK activity. Chronic high altitude hypoxia increases Rho/ROCK signaling in PV of pregnant ewes which decreases cGMP‐mediated relaxation. HL059435, 075187