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Redox regulation of responses to hypoxia and NO‐cGMP signaling in pulmonary vascular pathophysiology
Author(s) -
Wolin Michael S.,
Gupte Sachin A.,
Mingone Christopher J.,
Neo Boon Hwa,
Gao Qun,
Ahmad Mansoor
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05557.x
Subject(s) - hypoxia (environmental) , pathophysiology , signal transduction , redox , chemistry , microbiology and biotechnology , medicine , biology , biochemistry , oxygen , organic chemistry
Pulmonary vascular responses elicited by hypoxia and NO‐cGMP signaling are potentially influenced by ROS and redox mechanisms that change during the progression of disease processes. Our studies in endothelium‐rubbed bovine pulmonary arteries suggest increased glucose‐6‐phosphate dehydrogenase levels (compared to coronary arteries) seem to maintain a tonic peroxide‐mediated relaxation removed by hypoxia through NADPH fueling superoxide generation from Nox oxidase. The activities of glucose‐6‐phosphate dehydrogenase, oxidases (i.e., Nox4), and systems metabolizing superoxide and peroxide markedly influence hypoxic pulmonary vasoconstriction (HPV). Activation of soluble guanylate cyclase and cGMP protein kinase seems to participate in peroxide‐elicited relaxation. Endogenous NO helps maintain low pulmonary arterial pressure and suppresses HPV. Multiple redox processes potentially occurring during the progression of pulmonary hypertension may also attenuate NO‐mediated relaxation beyond its scavenging by superoxide, including oxidation of guanylate cyclase heme and thiols normally maintained by cytosolic NADPH redox control.