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NITRIC OXIDE (NO)‐INDUCED RELAXATION IN PULMONARY VESSELS OF EWES EXPOSED TO CHRONIC HIGH ALTITUDE HYPOXIA IS THROUGH A cGMP‐INDEPENDENT, Na+‐K+‐ATPase‐MEDIATED MECHANISM
Author(s) -
Chai Edward Ekmaha,
Negash Sewite,
Gao Yuasheng,
Longo Lawrence,
Raj Usha
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.1173.15
Subject(s) - nitric oxide , ouabain , chemistry , endocrinology , medicine , hypoxia (environmental) , atpase , hypoxic pulmonary vasoconstriction , endothelin 1 , pulmonary hypertension , biology , biochemistry , oxygen , receptor , enzyme , sodium , organic chemistry
Purpose. To determine alterations in NO mediated relaxation in pulmonary vessels of pregnant ewes exposed to chronic high altitude hypoxia (HAH). Methods. Isolated intrapulmonary vessels from pregnant ewes exposed to HAH or from matched sea‐level controls were preconstricted with endothelin‐1 and relaxed to DETA‐NONOate, a nitric oxide donor. Roles of guanylate cyclase; cGMP‐dependent protein kinase, PKG; Na+‐K+‐ATPase; and sarcoplasmic reticulum Ca2+‐ATPase, SERCA; were assessed by determining DETA‐NONOate‐mediated relaxation in the presence of the various inhibitors. Results. We found that relaxation to DETA‐NONATE in HAH vessels was decreased compared to controls. In the presence of ODQ, relaxation of HAH vessels to the NO donor was decreased in arteries but unchanged in veins, indicating that in the HAH veins, NO was mediating relaxation by a cGMP‐independent mechanism. The cGMP‐independent relaxation in veins was abolished with the addition of ouabain but not by thapsigargin, indicating that NO was mediating relaxation by activating Na+‐K+‐ATPase. Western blot analysis showed increased protein expression of Na+‐K+‐ATPase. Conclusion. Following exposure to chronic high altitude hypoxia, the relaxation responses to NO in intrapulmonary vessels of pregnant ewes are differentially altered. In veins, NO induced relaxation is decreased and is no longer mediated by activation of guanylate cyclase but occurs through activation of Na+‐K+‐ATPase. In arteries, NO‐mediated relaxation is also decreased but is still mediated via cGMP.