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PMID: 18315496 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Oxidant and redox signaling in vascular oxygen sensing: implications for systemic and pulmonary hypertension.

Antioxidants & redox signaling ·Vol. 10 ·No. 6 ·2008-06-00 ·Pages 1137-52

Gupte SA, Wolin MS

Abstract

It has been well known for >100 years that systemic blood vessels dilate in response to decreases in oxygen tension (hypoxia; low PO2), and this response appears to be critical to supply blood to the stressed organ. Conversely, pulmonary vessels constrict to a decrease in alveolar PO2 to maintain a balance in the ventilation-to-perfusion ratio. Currently, although little question exists that the PO2 affects vascular reactivity and vascular smooth muscle cells (VSMCs) act as oxygen sensors, the molecular mechanisms involved in modulating the vascular reactivity are still not clearly understood. Many laboratories, including ours, have suggested that the intracellular calcium concentration ([Ca2+]i), which regulates vasomotor function, is controlled by free radicals and redox signaling, including NAD(P)H and glutathione (GSH) redox. In this review article, therefore, we discuss the implications of redox and oxidant alterations seen in pulmonary and systemic hypertension, and how key targets that control [Ca2+]i, such as ion channels, Ca2+ release from internal stores and uptake by the sarcoplasmic reticulum, and the Ca2+ sensitivity to the myofilaments, are regulated by changes in intracellular redox and oxidants associated with vascular PO2sensing in physiologic or pathophysiologic conditions.

MeSH Terms
Hypertension/etiology,metabolism Hypertension, Pulmonary/etiology,metabolism Hypoxia/complications,metabolism,physiopathology Muscle, Smooth, Vascular/cytology,metabolism Oxidants/metabolism Oxidation-Reduction Oxidative Stress Oxygen/blood Pulmonary Artery/physiopathology Signal Transduction Vasoconstriction
Chemicals
Oxidants Oxygen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gupte Sachin A
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA. sachin_gupte@nymc.edu
Wolin Michael S
References (173)
173 references, click to expand
  1. Site of hypoxic pulmonary vasoconstriction.
    Chest. 1985 Oct;88(4 Suppl):240S-245S PMID: 4042730
  2. Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators.
    Circ Res. 2002 Sep 6;91(5):406-13 PMID: 12215489
  3. Ion channels in pulmonary arterial hypertension.
    Prog Cardiovasc Dis. 2002 Sep-Oct;45(2):81-114 PMID: 12411972
  4. Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels.
    Circ Res. 2003 Feb 7;92(2):151-8 PMID: 12574142
  5. Effects of hypoxia on isometric force, intracellular Ca(2+), pH, and energetics in porcine coronary artery.
    Circ Res. 2000 Apr 28;86(8):862-70 PMID: 10785508
  6. Hypoxia promotes relaxation of bovine coronary arteries through lowering cytosolic NADPH.
    Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2228-38 PMID: 16415080
  7. Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats.
    Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L665-72 PMID: 12959926
  8. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing.
    Circ Res. 2001 Jun 22;88(12):1259-66 PMID: 11420302
  9. Role of prostaglandins in mediating differences in human internal mammary and radial artery relaxation elicited by hypoxia.
    J Pharmacol Exp Ther. 2004 Nov;311(2):510-8 PMID: 15229231
  10. Estradiol attenuates hypoxia-induced pulmonary endothelin-1 gene expression.
    Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L86-93 PMID: 12060564
  11. Regulation of NADPH oxidases: the role of Rac proteins.
    Circ Res. 2006 Mar 3;98(4):453-62 PMID: 16514078
  12. Cysteine redox sensor in PKGIa enables oxidant-induced activation.
    Science. 2007 Sep 7;317(5843):1393-7 PMID: 17717153
  13. Pulmonary artery NADPH-oxidase is activated in hypoxic pulmonary vasoconstriction.
    Am J Respir Cell Mol Biol. 1996 Nov;15(5):633-44 PMID: 8918370
  14. Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension.
    Circ Res. 2006 Feb 3;98(2):209-17 PMID: 16357305
  15. Role of HIF-1 in physiological adaptation of the carotid body during chronic hypoxia.
    Adv Exp Med Biol. 2003;536:593-601 PMID: 14635717
  16. Quantitative mapping of oxidation-sensitive cysteine residues in SERCA in vivo and in vitro by HPLC-electrospray-tandem MS: selective protein oxidation during biological aging.
    Biochem J. 2006 Mar 15;394(Pt 3):605-15 PMID: 16307534
  17. Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle.
    Circ Res. 1997 Jan;80(1):82-7 PMID: 8978326
  18. Thiol oxidation activates a novel redox-regulated coronary vasodilator mechanism involving inhibition of Ca2+ influx.
    Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2359-65 PMID: 11073838
  19. Guanylyl cyclases and signaling by cyclic GMP.
    Pharmacol Rev. 2000 Sep;52(3):375-414 PMID: 10977868
  20. NADH and NAD modulates Ca(2+)-activated K+ channels in small pulmonary arterial smooth muscle cells of the rabbit.
    Pflugers Arch. 1994 Jun;427(3-4):378-80 PMID: 8072860
  21. Superoxide-producing cytochrome b. Enzymatic and electron paramagnetic resonance properties of cytochrome b558 purified from neutrophils.
    J Biol Chem. 1993 Feb 25;268(6):4025-31 PMID: 8382686
  22. Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries.
    Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H13-21 PMID: 15345489
  23. Reduction of Ca(2+) channel activity by hypoxia in human and porcine coronary myocytes.
    Cardiovasc Res. 2002 Jan;53(1):97-104 PMID: 11744017
  24. Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries.
    Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L322-33 PMID: 12665465
  25. High pressure induces superoxide production in isolated arteries via protein kinase C-dependent activation of NAD(P)H oxidase.
    Circulation. 2003 Sep 9;108(10):1253-8 PMID: 12874194
  26. Genetic polymorphism at nine microsatellite loci in four high altitude Himalayan desert human populations.
    Forensic Sci Int. 2002 Jun 25;127(1-2):150-5 PMID: 12173571
  27. Metabolic factors that influence contractility of vascular smooth muscle.
    Bull N Y Acad Med. 1966 Nov;42(11):996-1006 PMID: 5232128
  28. Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation.
    Circulation. 2006 Jun 20;113(24):2818-25 PMID: 16769910
  29. Sleep disordered breathing and hypertension.
    J Clin Sleep Med. 2005 Oct 15;1(4):401-4 PMID: 17564410
  30. NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release.
    Circ Res. 2004 Mar 5;94(4):478-86 PMID: 14699012
  31. Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9488-93 PMID: 12878719
  32. O(2) sensing in hypoxic pulmonary vasoconstriction: the mitochondrial door re-opens.
    Respir Physiol Neurobiol. 2002 Aug 22;132(1):81-91 PMID: 12126697
  33. Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue.
    Exp Physiol. 1995 Sep;80(5):825-34 PMID: 8546871
  34. Renin activity and blood pressure in response to chronic episodic hypoxia.
    Hypertension. 1999 Aug;34(2):309-14 PMID: 10454459
  35. Crystal structure of an oxygen-binding heme domain related to soluble guanylate cyclases.
    Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12854-9 PMID: 15326296
  36. NADPH and heme redox modulate pulmonary artery relaxation and guanylate cyclase activation by NO.
    Am J Physiol. 1999 Dec;277(6):L1124-32 PMID: 10600882
  37. The coronary circulation in diabetes: influence of reactive oxygen species on K+ channel-mediated vasodilation.
    Vascul Pharmacol. 2002 Jan;38(1):43-9 PMID: 12378822
  38. Oxygen and cyclic nucleotides in human umbilical artery.
    Proc Natl Acad Sci U S A. 1975 Oct;72(10):3883-7 PMID: 172888
  39. NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium.
    Am J Physiol. 1994 Jun;266(6 Pt 2):H2568-72 PMID: 8024019
  40. Role of a novel KCa opener in regulating K+ channels of hypoxic human pulmonary vascular cells.
    Am J Respir Cell Mol Biol. 1999 Apr;20(4):737-45 PMID: 10101006
  41. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins.
    Circulation. 2001 Aug 14;104(7):790-5 PMID: 11502704
  42. Superoxide released to high intra-arteriolar pressure reduces nitric oxide-mediated shear stress- and agonist-induced dilations.
    Circ Res. 1998 Nov 2;83(9):960-5 PMID: 9797346
  43. Mitochondrial criticality: a new concept at the turning point of life or death.
    Biochim Biophys Acta. 2006 Feb;1762(2):232-40 PMID: 16242921
  44. Mitochondrial reactive oxygen species and c-Src play a critical role in hypoxic response in vascular smooth muscle cells.
    Cardiovasc Res. 2005 Sep 1;67(4):714-22 PMID: 15913578
  45. Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH.
    Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L159-73 PMID: 16002998
  46. Glucose-6-phosphate dehydrogenase: a "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress.
    FASEB J. 1994 Feb;8(2):174-81 PMID: 8119488
  47. S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide.
    Nat Med. 2004 Nov;10(11):1200-7 PMID: 15489859
  48. The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
    Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12155-60 PMID: 12218169
  49. Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4715-9 PMID: 7753871
  50. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction.
    Am J Physiol. 1992 Apr;262(4 Pt 1):C882-90 PMID: 1566816
  51. Calcium sparks in smooth muscle.
    Am J Physiol Cell Physiol. 2000 Feb;278(2):C235-56 PMID: 10666018
  52. Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca(2+)-activated K(+)-channel opener.
    Am J Physiol. 1998 Feb;274(2):L186-95 PMID: 9486202
  53. Distinct pathways of Ca(2+) sensitization in porcine coronary artery: effects of Rho-related kinase and protein kinase C inhibition on force and intracellular Ca(2+).
    Circ Res. 2001 Jun 22;88(12):1283-90 PMID: 11420305
  54. Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension.
    Cardiovasc Res. 2007 Jun 1;74(3):377-87 PMID: 17346686
  55. Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta.
    Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1495-500 PMID: 15371261
  56. Contrasting effects of hypoxia on cytosolic Ca2+ spikes in conduit and resistance myocytes of the rabbit pulmonary artery.
    J Physiol. 1996 Oct 1;496 ( Pt 1):103-9 PMID: 8910199
  57. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats.
    Circulation. 2003 Apr 22;107(15):2037-44 PMID: 12695303
  58. Capacitative calcium entry: a central role in hypoxic pulmonary vasoconstriction?
    Am J Physiol Lung Cell Mol Physiol. 2005 Jul;289(1):L2-4 PMID: 15955897
  59. Redox regulation of cardiac calcium channels and transporters.
    Cardiovasc Res. 2006 Jul 15;71(2):310-21 PMID: 16581043
  60. EVIDENCE FOR TISSUE OXYGEN DEMAND AS THE MAJOR FACTOR CAUSING AUTOREGULATION.
    Circ Res. 1964 Aug;15:SUPPL:60-9 PMID: 14206321
  61. Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-sensitive ion channels.
    Cell Calcium. 2003 Sep;34(3):211-29 PMID: 12887969
  62. The good, the bad and the ugly in oxygen-sensing: ROS, cytochromes and prolyl-hydroxylases.
    Cardiovasc Res. 2006 Jul 15;71(2):195-207 PMID: 16740253
  63. Response of small pulmonary arteries to unilobar hypoxia and hypercapnia.
    Circ Res. 1966 Aug;19(2):426-40 PMID: 5914855
  64. Diversity in mitochondrial function explains differences in vascular oxygen sensing.
    Circ Res. 2002 Jun 28;90(12):1307-15 PMID: 12089069
  65. Mitochondrial reactive oxygen species trigger calcium increases during hypoxia in pulmonary arterial myocytes.
    Circ Res. 2002 Oct 18;91(8):719-26 PMID: 12386149
  66. Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide.
    J Clin Invest. 1995 Apr;95(4):1798-807 PMID: 7706486
  67. A specific and potent pressor effect of hypoxia in patients with sleep apnea.
    Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1240-5 PMID: 1443878
  68. Effect of cyanide on oxygen tension-dependent mechanical tension in rabbit aorta.
    Circ Res. 1979 Mar;44(3):368-78 PMID: 761319
  69. A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes.
    J Biol Chem. 2001 Oct 5;276(40):37594-601 PMID: 11483596
  70. Inhibition of hypoxic pulmonary vasoconstriction by diphenyleneiodonium.
    Biochem Pharmacol. 1991 Sep 12;42(7):R9-12 PMID: 1930255
  71. NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea.
    Am J Respir Crit Care Med. 2005 Oct 1;172(7):921-9 PMID: 15994465
  72. Pentose phosphate pathway coordinates multiple redox-controlled relaxing mechanisms in bovine coronary arteries.
    Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2316-26 PMID: 12933338
  73. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model.
    J Clin Invest. 1997 Jan 1;99(1):106-9 PMID: 9011563
  74. Adenosine and metabolic regulation of coronary blood flow in dogs with renal hypertension.
    Hypertension. 1983 Nov-Dec;5(6):943-50 PMID: 6228529
  75. ATPase activity, IF1 content, and proton conductivity of ESMP from control and ischemic slow and fast heart-rate hearts.
    J Bioenerg Biomembr. 1995 Aug;27(4):459-66 PMID: 8595981
  76. Methaemoglobin and erythrocyte reducing systems in high-altitude natives.
    Ann Hum Biol. 1979 Nov-Dec;6(6):585-92 PMID: 583558
  77. c-Src induces phosphorylation and translocation of p47phox: role in superoxide generation by angiotensin II in human vascular smooth muscle cells.
    Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):981-7 PMID: 12663375
  78. Induction of the glucose-6-phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells.
    FEBS Lett. 2004 Jul 2;569(1-3):256-60 PMID: 15225644
  79. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension.
    Circulation. 2006 Jun 6;113(22):2630-41 PMID: 16735674
  80. Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice.
    Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H997-1006 PMID: 17384123
  81. Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation.
    Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12312-7 PMID: 17636120
  82. Binding of pyridine nucleotide coenzymes to the beta-subunit of the voltage-sensitive K+ channel.
    J Biol Chem. 2001 Apr 13;276(15):11812-20 PMID: 11278398
  83. High altitude adaptation in Tibetans.
    High Alt Med Biol. 2006 Fall;7(3):193-208 PMID: 16978132
  84. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure.
    Circulation. 2006 Oct 24;114(17):1883-91 PMID: 17060398
  85. Properties of a superoxide anion-generating microsomal NADH oxidoreductase, a potential pulmonary artery PO2 sensor.
    Am J Physiol. 1994 Dec;267(6 Pt 1):L823-31 PMID: 7810686
  86. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans.
    Hypertension. 2001 Dec 1;38(6):1307-10 PMID: 11751708
  87. Role of pentose phosphate pathway-derived NADPH in hypoxic pulmonary vasoconstriction.
    Pulm Pharmacol Ther. 2006;19(4):303-9 PMID: 16203165
  88. Stretch enhances contraction of bovine coronary arteries via an NAD(P)H oxidase-mediated activation of the extracellular signal-regulated kinase mitogen-activated protein kinase cascade.
    Circ Res. 2003 Jan 10;92(1):23-31 PMID: 12522117
  89. Oxygen sensors in hypoxic pulmonary vasoconstriction.
    Cardiovasc Res. 2006 Sep 1;71(4):620-9 PMID: 16765922
  90. Characteristics and actions of NAD(P)H oxidase on the sarcoplasmic reticulum of coronary artery smooth muscle.
    Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1136-44 PMID: 16227345
  91. Influence of hypoxia on the longitudinal distribution of pulmonary vascular resistance.
    J Appl Physiol Respir Environ Exerc Physiol. 1978 Apr;44(4):493-8 PMID: 640912
  92. Calmodulin binding and inhibition of cardiac muscle calcium release channel (ryanodine receptor).
    J Biol Chem. 2001 Jun 8;276(23):20144-53 PMID: 11274202
  93. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel.
    Science. 2004 Dec 17;306(5704):2093-7 PMID: 15528406
  94. Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats.
    Circ Res. 2007 Mar 30;100(6):923-9 PMID: 17332430
  95. Mutations in the Kv beta 2 binding site for NADPH and their effects on Kv1.4.
    J Biol Chem. 2001 Jan 5;276(1):738-41 PMID: 11024060
  96. Cardiovascular consequences of sleep-related breathing disorders.
    Heart Dis. 2002 Sep-Oct;4(5):296-305 PMID: 12350242
  97. A conserved family of prolyl-4-hydroxylases that modify HIF.
    Science. 2001 Nov 9;294(5545):1337-40 PMID: 11598268
  98. A redox-based O2 sensor in rat pulmonary vasculature.
    Circ Res. 1993 Dec;73(6):1100-12 PMID: 8222081
  99. Hypoxia, energy state and pulmonary vasomotor tone.
    Respir Physiol Neurobiol. 2002 Aug 22;132(1):55-67 PMID: 12126695
  100. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression.
    J Appl Physiol (1985). 2001 Sep;91(3):1421-30 PMID: 11509544
  101. Mechanism of physiological hypoxia-induced depression of vascular smooth muscle contraction.
    Am J Physiol. 1980 Jun;238(6):H761-9 PMID: 6247924
  102. Redox status in the control of pulmonary vascular tone.
    Herz. 1986 Jun;11(3):127-41 PMID: 3017827
  103. Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system.
    N Engl J Med. 1996 Feb 8;334(6):374-81 PMID: 8538710
  104. Hypoxia and smooth muscle function: key regulatory events during metabolic stress.
    J Physiol. 1998 Jun 1;509 ( Pt 2):315-25 PMID: 9575282
  105. Hypoxic vasoconstriction in pulmonary arterioles and venules.
    J Appl Physiol (1985). 1997 Apr;82(4):1084-90 PMID: 9104843
  106. Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats.
    Hypertension. 1992 Jun;19(6 Pt 1):555-61 PMID: 1592450
  107. The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels.
    FASEB J. 1995 Feb;9(2):183-9 PMID: 7781921
  108. Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat.
    J Appl Physiol (1985). 2006 Mar;100(3):996-1002 PMID: 16322374
  109. Differential regulation of voltage-gated K+ channels by oxidized and reduced pyridine nucleotide coenzymes.
    Am J Physiol Cell Physiol. 2005 Feb;288(2):C366-76 PMID: 15469953
  110. A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent.
    Am J Physiol. 1998 Dec;275(6):L1019-25 PMID: 9843837
  111. Angiotensin II and endothelin-1 regulate MAP kinases through different redox-dependent mechanisms in human vascular smooth muscle cells.
    J Hypertens. 2004 Jun;22(6):1141-9 PMID: 15167449
  112. Derepression of pathological cardiac genes by members of the CaM kinase superfamily.
    Cardiovasc Res. 2007 Mar 1;73(4):667-77 PMID: 17217938
  113. Calcium signalling: dynamics, homeostasis and remodelling.
    Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29 PMID: 12838335
  114. Hypoxic relaxation in functionally intact cattle coronary artery segments involves K+ ATP channels.
    J Pharmacol Exp Ther. 1995 Dec;275(3):1219-26 PMID: 8531084
  115. Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea.
    Neuroscience. 2004;126(2):313-23 PMID: 15207349
  116. Actions of sulfhydryl reagents on single ryanodine receptor Ca(2+)-release channels from sheep myocardium.
    Am J Physiol. 1997 Jun;272(6 Pt 1):C1908-18 PMID: 9227420
  117. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.
    J Am Coll Cardiol. 2007 Jun 26;49(25):2379-93 PMID: 17599600
  118. Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels.
    Am J Physiol Lung Cell Mol Physiol. 2005 Jul;289(1):L5-L13 PMID: 15722380
  119. Hypoxia and Rho/Rho-kinase signaling. Lung development versus hypoxic pulmonary hypertension.
    Adv Exp Med Biol. 2003;543:127-37 PMID: 14713118
  120. Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats.
    Am J Respir Cell Mol Biol. 1999 Apr;20(4):620-30 PMID: 10100993
  121. Modulation of recombinant human cardiac L-type Ca2+ channel alpha1C subunits by redox agents and hypoxia.
    J Physiol. 1999 Feb 1;514 ( Pt 3):629-37 PMID: 9882735
  122. Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells.
    Circ Res. 2006 Oct 27;99(9):970-8 PMID: 17008601
  123. Functional consequences of sulfhydryl modification in the pore-forming subunits of cardiovascular Ca2+ and Na+ channels.
    Circ Res. 1995 Mar;76(3):325-34 PMID: 7859379
  124. Oxygen activates the Rho/Rho-kinase pathway and induces RhoB and ROCK-1 expression in human and rabbit ductus arteriosus by increasing mitochondria-derived reactive oxygen species: a newly recognized mechanism for sustaining ductal constriction.
    Circulation. 2007 Apr 3;115(13):1777-88 PMID: 17353442
  125. Role of calcium ions in regulation of mammalian intramitochondrial metabolism.
    Physiol Rev. 1990 Apr;70(2):391-425 PMID: 2157230
  126. Modulation of voltage-dependent K+ channel by redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit.
    Pflugers Arch. 1997 Nov;434(6):764-71 PMID: 9306010
  127. Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats.
    J Appl Physiol (1985). 2001 May;90(5):2007-13; discussion 2000 PMID: 11299297
  128. Hypoxic vasoconstriction in intact lungs: a role for NADPH oxidase-derived H(2)O(2)?
    Am J Physiol Lung Cell Mol Physiol. 2000 Oct;279(4):L683-90 PMID: 11000128
  129. Rho kinase is an effector underlying Ca2+-desensitizing hypoxic relaxation in porcine coronary artery.
    Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H23-9 PMID: 17416603
  130. Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion.
    Eur J Biochem. 1990 Sep 24;192(3):683-8 PMID: 1976516
  131. Regulation of L-type calcium channels of vascular smooth muscle cells.
    J Mol Cell Cardiol. 1995 Jan;27(1):75-91 PMID: 7760390
  132. Redox agents as a link between hypoxia and the responses of ionic channels in rabbit pulmonary vascular smooth muscle.
    Exp Physiol. 1995 Sep;80(5):835-42 PMID: 8546872
  133. Inhaled Rho kinase inhibitors are potent and selective vasodilators in rat pulmonary hypertension.
    Am J Respir Crit Care Med. 2005 Mar 1;171(5):494-9 PMID: 15563635
  134. Indications to an NADPH oxidase as a possible pO2 sensor in the rat carotid body.
    FEBS Lett. 1989 Oct 9;256(1-2):75-8 PMID: 2806553
  135. Identification of renox, an NAD(P)H oxidase in kidney.
    Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8010-4 PMID: 10869423
  136. Subcellular localization of NAD(P)H oxidase(s) in human neutrophilic polymorphonuclear leucocytes.
    Biochem J. 1978 Oct 15;176(1):175-8 PMID: 728106
  137. Hypoxic pulmonary vasoconstriction persists in the human transplanted lung.
    Clin Sci (Lond). 1987 Mar;72(3):283-7 PMID: 3545645
  138. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?
    Hypertension. 2004 Sep;44(3):248-52 PMID: 15262903
  139. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase.
    Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7944-9 PMID: 10393927
  140. Function of h(2)o(2), myeloperoxidase, and hexose monophosphate shunt enzymes in phagocytizing cells from different species.
    Infect Immun. 1970 Apr;1(4):338-44 PMID: 16557739
  141. AT1 receptor blocker added to ACE inhibitor provides benefits at advanced stage of hypertensive diastolic heart failure.
    Hypertension. 2004 Mar;43(3):686-91 PMID: 14757777
  142. Thiol oxidation inhibits nitric oxide-mediated pulmonary artery relaxation and guanylate cyclase stimulation.
    Am J Physiol Lung Cell Mol Physiol. 2006 Mar;290(3):L549-57 PMID: 16272175
  143. Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(-) and systolic blood pressure in mice.
    Circ Res. 2001 Aug 31;89(5):408-14 PMID: 11532901
  144. Physiological roles and properties of potassium channels in arterial smooth muscle.
    Am J Physiol. 1995 Apr;268(4 Pt 1):C799-822 PMID: 7733230
  145. Oxygen-elicited responses in calf coronary arteries: role of H2O2 production via NADH-derived superoxide.
    Am J Physiol. 1996 Mar;270(3 Pt 2):H1044-53 PMID: 8780202
  146. Molecular determinants of drug binding and action on L-type calcium channels.
    Annu Rev Pharmacol Toxicol. 1997;37:361-96 PMID: 9131258
  147. Redox signaling in oxygen sensing by vessels.
    Respir Physiol Neurobiol. 2002 Aug 22;132(1):121-30 PMID: 12126700
  148. Epiandrosterone, a metabolite of testosterone precursor, blocks L-type calcium channels of ventricular myocytes and inhibits myocardial contractility.
    J Mol Cell Cardiol. 2002 Jun;34(6):679-88 PMID: 12054855
  149. Oxygen tension sensors in vascular smooth muscle.
    Adv Exp Med Biol. 1977;78:101-15 PMID: 899910
  150. Modulation of vascular smooth muscle signaling by reactive oxygen species.
    Physiology (Bethesda). 2006 Aug;21:269-80 PMID: 16868316
  151. H2O2 and cGMP may function as an O2 sensor in the pulmonary artery.
    J Appl Physiol (1985). 1989 Jan;66(1):167-70 PMID: 2537281
  152. Inhibition of cGMP-associated pulmonary arterial relaxation to H2O2 and O2 by ethanol.
    Am J Physiol. 1990 May;258(5 Pt 2):H1267-73 PMID: 1970924
  153. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels.
    Science. 1990 Mar 16;247(4948):1341-4 PMID: 2107575
  154. Inhibitors of pentose phosphate pathway cause vasodilation: involvement of voltage-gated potassium channels.
    J Pharmacol Exp Ther. 2002 Apr;301(1):299-305 PMID: 11907187
  155. Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel.
    Mol Pharmacol. 1998 Mar;53(3):497-503 PMID: 9495817
  156. Report of the Hypertension Task Force of the National Heart, Lung, and Blood Institute. Current research and recommendations from the Subgroup on Local Hemodynamics.
    Hypertension. 1980 May-Jun;2(3):342-69 PMID: 6993361
  157. Inhibitors of oxidative ATP production cause transient vasoconstriction and block subsequent pressor responses in rat lungs.
    Circ Res. 1981 Mar;48(3):393-400 PMID: 7460212
  158. Fine tuning the HIF-1 'global' O2 sensor for hypobaric hypoxia in Andean high-altitude natives.
    Bioessays. 2003 May;25(5):515-9 PMID: 12717822
  159. The biology of cyclic GMP-dependent protein kinases.
    J Biol Chem. 2005 Jan 7;280(1):1-4 PMID: 15545263
  160. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists.
    Nature. 1984 Oct 11-17;311(5986):538-44 PMID: 6207437
  161. Different mechanisms of hypoxic relaxation in canine coronary arteries and rat abdominal aortas.
    J Cardiovasc Pharmacol. 1992;20 Suppl 12:S117-9 PMID: 1282944
  162. Potential role of NADH oxidoreductase-derived reactive O2 species in calf pulmonary arterial PO2-elicited responses.
    Am J Physiol. 1995 Nov;269(5 Pt 1):L637-44 PMID: 7491983
  163. Divergent roles of glycolysis and the mitochondrial electron transport chain in hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor.
    J Physiol. 2001 Oct 1;536(Pt 1):211-24 PMID: 11579170
  164. Different modulation of Ca-activated K channels by the intracellular redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit.
    Pflugers Arch. 1995 Jul;430(3):308-14 PMID: 7491253
  165. Ca2+ channels, Ca2+ sparks, and regulation of arterial smooth muscle function.
    Z Kardiol. 2000;89 Suppl 2:15-9 PMID: 10769399
  166. Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of reactive oxygen species.
    J Appl Physiol (1985). 2006 Sep;101(3):1000-1; author reply 1004-5 PMID: 16969918
  167. Dependence of Ca2+ channel currents on endogenous and exogenous sources of ATP in portal vein smooth muscle.
    Am J Physiol. 1997 Feb;272(2 Pt 2):H987-94 PMID: 9124463
  168. Guanylate cyclase and the .NO/cGMP signaling pathway.
    Biochim Biophys Acta. 1999 May 5;1411(2-3):334-50 PMID: 10320667
  169. An NADPH oxidase superoxide-generating system in the rabbit aorta.
    Am J Physiol. 1995 Jun;268(6 Pt 2):H2274-80 PMID: 7611477
  170. Acute oxygen-sensing mechanisms.
    N Engl J Med. 2005 Nov 10;353(19):2042-55 PMID: 16282179
  171. Differential oxygen sensitivity of calcium channels in rabbit smooth muscle cells of conduit and resistance pulmonary arteries.
    J Physiol. 1996 Mar 1;491 ( Pt 2):511-8 PMID: 8866874
  172. Sites of superoxide anion production detected by lucigenin in calf pulmonary artery smooth muscle.
    Am J Physiol. 1994 Dec;267(6 Pt 1):L815-22 PMID: 7810685
  173. Steady-state vascular responses to graded hypoxia in isolated lungs of five species.
    J Appl Physiol Respir Environ Exerc Physiol. 1981 Nov;51(5):1214-9 PMID: 7298460
Article Info
Journal
Antioxidants & redox signaling
Abbr.
Antioxid Redox Signal
ISSN
1523-0864
DOI
10.1089/ars.2007.1995
Email
sachin_gupte@nymc.edu
Published
2008-06-00
Pages
1137-52
Language
English
Region
United States
NLM ID
100888899
PMCID
PMC2443404
Subset
IM
Grants
NHLBI NIH HHS · R01 HL031069 · United States
NHLBI NIH HHS · P01 HL043023-17 · United States
NHLBI NIH HHS · HL085352 · United States
NHLBI NIH HHS · R01 HL066331 · United States
NHLBI NIH HHS · R01 HL085352 · United States
NHLBI NIH HHS · P01 HL043023-170002 · United States
NHLBI NIH HHS · R01 HL132574 · United States
NHLBI NIH HHS · P01 HL043023 · United States
NHLBI NIH HHS · R01 HL031069-23 · United States
NHLBI NIH HHS · R01 HL066331-07 · United States
NHLBI NIH HHS · HL31069 · United States
NHLBI NIH HHS · HL66331 · United States
NHLBI NIH HHS · R01 HL085352-01A2 · United States
PHS HHS · H43023 · United States
External Links
PubMed source DOI: 10.1089/ars.2007.1995 PMC Full Text View journal details
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