title: Redox regulation of guanylate cyclase and protein kinase G in vascular responses to hypoxia.
abstract: The production of cGMP by the soluble form of guanylate cyclase (sGC) in bovine pulmonary arteries (BPA) is controlled by cytosolic NADPH maintaining reduced thiol and heme sites on sGC needed for activation by NO, and the levels of Nox oxidase-derived superoxide and peroxide that influence pathways regulating sGC activity. Our recent studies in BPA suggest that the activities of peroxide metabolizing pathways in vascular smooth muscle potentially determine the balance between sGC stimulation by peroxide and a cGMP-independent activation of cGMP-dependent protein kinase (PKG) by a disulfide-mediated subunit dimerization. Cytosolic NADPH oxidation also appears to function in BPA through its influence on protein thiol redox control as an additional mechanism promoting vascular relaxation through PKG activation. These processes regulating PKG may participate in decreases in peroxide and increases in NADPH associated with contraction of BPA to hypoxia and in cytosolic NADPH oxidation potentially mediating bovine coronary artery relaxation to hypoxia.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, United States.
authors.forename: Boon Hwa
authors.initials: BH
authors.lastname: Neo
authors.forename: Sharath
authors.initials: S
authors.lastname: Kandhi
authors.forename: Mansoor
authors.initials: M
authors.lastname: Ahmad
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolin
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000201:enzymology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide; D000860:Hypoxia / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction
chemical_list: D006861:Hydrogen Peroxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase