(Circulation. 1997;96:3647-3654.)
© 1997 American Heart Association, Inc.
Articles |
Ca2+ Release From Intracellular Stores Is an Initial Step in Hypoxic Pulmonary Vasoconstriction of Rat Pulmonary Artery Resistance Vessels
From the Department of Physiology, University of Florida College of Medicine, Gainesville (C.H.G.), and the Division of Pediatric Cardiology, Department of Pediatrics, University of Miami (Fla) School of Medicine (H.G.).
Correspondence to Craig H. Gelband, Department of Physiology, University of Florida College of Medicine, PO Box 100274, Gainesville (C.H.G.), FL 32610. E-mail gelband{at}phys.med.ufl.edu
Background A reduction in oxygen tension in the lungs is believed to inhibit a voltage-dependent K+ (Kv) current, which is thought to result in membrane depolarization leading to hypoxic pulmonary vasoconstriction (HPV). However, the direct mechanism by which hypoxia inhibits Kv current is not understood.
Methods and Results Experiments were performed on rat pulmonary artery resistance vessels and single smooth muscle cells isolated from these vessels to examine the role of Ca2+ release from intracellular stores in initiating HPV. In contractile experiments, hypoxic challenge of endothelium-denuded rat pulmonary artery resistance vessels caused either a sustained or transient contraction in Ca2+-containing or Ca2+-free solution, respectively (n=44 vessels from 11 animals). When the ring segments were treated with either thapsigargin (5 µmol/L), ryanodine (5 µmol/L), or cyclopiazonic acid (5 µmol/L) in Ca2+-containing or Ca2+-free solution, a significant increase in pulmonary arterial tone was observed (n=44 vessels from 11 animals). Subsequent hypoxic challenge in the presence of each agent produced no further increase in tone (n=44 vessels from 11 animals). In isolated pulmonary resistance artery cells loaded with fura 2, hypoxic challenge, thapsigargin, ryanodine, and cyclopiazonic acid resulted in a significant increase in [Ca2+]i (n=18 cells from 6 animals) and depolarization of the resting membrane potential (n=22 cells from 6 animals). However, with prior application of thapsigargin, ryanodine, or cyclopiazonic acid, a hypoxic challenge produced no further change in [Ca2+]i (n=18 from 6 animals) or membrane potential (n=22 from 6 animals). Finally, application of an anti-Kv1.5 antibody increased [Ca2+]i and caused membrane depolarization. Subsequent hypoxic challenge resulted in a further increase in [Ca2+]i with no effect on membrane potential (n=16 cells from 4 animals).
Conclusions In rat pulmonary artery resistance vessels, an initial event in HPV is a release of Ca2+ from intracellular stores. This rise in [Ca2+]i causes inhibition of voltage-dependent K+ channels (possibly Kv1.5), membrane depolarization, and an increase in pulmonary artery tone.
Key Words: hypoxia • calcium • sarcoplasmic reticulum • potassium •
This article has been cited by other articles:
 |
|
 |
|
  G. Zhao, A. Adebiyi, Q. Xi, and J. H. Jaggar Hypoxia reduces KCa channel activity by inducing Ca2+ spark uncoupling in cerebral artery smooth muscle cells Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2122 - C2128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Y. Rochefort and E. D. Michelakis COUNTERPOINT: RELEASE OF AN ENDOTHELIUM-DERIVED VASOCONSTRICTOR AND RHOA/RHO KINASE-MEDIATED CALCIUM SENSITIZATION OF SMOOTH MUSCLE CELL CONTRACTION ARE NOT THE MAIN EFFECTORS FOR FULL AND SUSTAINED HPV J Appl Physiol, May 1, 2007; 102(5): 2072 - 2075. [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Olson, R. A. Dombkowski, M. J. Russell, M. M. Doellman, S. K. Head, N. L. Whitfield, and J. A. Madden Hydrogen sulfide as an oxygen sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic vasodilation J. Exp. Biol., October 15, 2006; 209(20): 4011 - 4023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Du, T. J. McMahon, Z.-S. Zhang, J. A. Stiber, G. Meissner, and J. P. Eu Excitation-Contraction Coupling in Airway Smooth Muscle J. Biol. Chem., October 6, 2006; 281(40): 30143 - 30151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Tsai, M. W. Turrentine, B. C. Sheridan, M. Wang, A. C. Fiore, J. W. Brown, and D. R. Meldrum Differential Effects of Phosphodiesterase-5 Inhibitors on Hypoxic Pulmonary Vasoconstriction and Pulmonary Artery Cytokine Expression Ann. Thorac. Surg., January 1, 2006; 81(1): 272 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Du, J. A. Stiber, P. B. Rosenberg, G. Meissner, and J. P. Eu Ryanodine Receptors in Muscarinic Receptor-mediated Bronchoconstriction J. Biol. Chem., July 15, 2005; 280(28): 26287 - 26294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Moudgil, E. D. Michelakis, and S. L. Archer Hypoxic pulmonary vasoconstriction J Appl Physiol, January 1, 2005; 98(1): 390 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Tsai, M. Wang, J. M. Pitcher, K. K. Meldrum, and D. R. Meldrum Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1215 - L1219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Tsai, M. Wang, M. W. Turrentine, Y. Mahomed, J. W. Brown, and D. R. Meldrum Hypoxic pulmonary vasoconstriction in cardiothoracic surgery: basic mechanisms to potential therapies Ann. Thorac. Surg., July 1, 2004; 78(1): 360 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bonnet, J.-P. Savineau, W. Barillot, E. Dubuis, C. Vandier, and P. Bonnet Role of Ca2+-sensitive K+ channels in the remission phase of pulmonary hypertension in chronic obstructive pulmonary diseases Cardiovasc Res, November 1, 2003; 60(2): 326 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-X. Wang, Y.-M. Zheng, I. Abdullaev, and M. I. Kotlikoff Metabolic inhibition with cyanide induces calcium release in pulmonary artery myocytes and Xenopus oocytes Am J Physiol Cell Physiol, February 1, 2003; 284(2): C378 - C388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olschewski, Z. Hong, D. P. Nelson, and E. K. Weir Graded response of K+ current, membrane potential, and [Ca2+]i to hypoxia in pulmonary arterial smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1143 - L1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Waypa, J. D. Marks, M. M. Mack, C. Boriboun, P. T. Mungai, and P. T. Schumacker Mitochondrial Reactive Oxygen Species Trigger Calcium Increases During Hypoxia in Pulmonary Arterial Myocytes Circ. Res., October 18, 2002; 91(8): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Remillard, W.-M. Zhang, L. A. Shimoda, and J. S. K. Sham Physiological properties and functions of Ca2+ sparks in rat intrapulmonary arterial smooth muscle cells Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L433 - L444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Morio and I. F. McMurtry Ca2+ release from ryanodine-sensitive store contributes to mechanism of hypoxic vasoconstriction in rat lungs J Appl Physiol, February 1, 2002; 92(2): 527 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Russell, N. J. Pelaez, C. S. Packer, M. E. Forster, and K. R. Olson Intracellular and extracellular calcium utilization during hypoxic vasoconstriction of cyclostome aortas Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1506 - R1513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Weissmann, F. Grimminger, A. Olschewski, and W. Seeger Hypoxic pulmonary vasoconstriction: a multifactorial response? Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L314 - L317. [Full Text] [PDF]
|
|
|
|
|
|
M. Dipp, P. C. G. Nye, and A. M. Evans Hypoxic release of calcium from the sarcoplasmic reticulum of pulmonary artery smooth muscle Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L318 - L325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Coppock, J. R. Martens, and M. M. Tamkun Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L1 - L12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Liu, J. S. K. Sham, L. A. Shimoda, and J. T. Sylvester Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L856 - L865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Platoshyn, V. A. Golovina, C. L. Bailey, A. Limsuwan, S. Krick, M. Juhaszova, J. E. Seiden, L. J. Rubin, and J. X.-J. Yuan Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1540 - C1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-X. WANG, P. K. DHULIPALA, and M. I. KOTLIKOFF Hypoxia inhibits the Na+/Ca2+ exchanger in pulmonary artery smooth muscle cells FASEB J, September 1, 2000; 14(12): 1731 - 1740. [Abstract] [Full Text]
|
|
|
|
|
|
J. S. K. Sham, B. R. Crenshaw Jr., L.-H. Deng, L. A. Shimoda, and J. T. Sylvester Effects of hypoxia in porcine pulmonary arterial myocytes: roles of KV channel and endothelin-1 Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L262 - L272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Simpson, J. E. van Eyk, and S. Iscoe Hypoxemia-induced modification of troponin I and T in canine diaphragm J Appl Physiol, February 1, 2000; 88(2): 753 - 760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Hulme, E. A. Coppock, A. Felipe, J. R. Martens, and M. M. Tamkun Oxygen Sensitivity of Cloned Voltage-Gated K+ Channels Expressed in the Pulmonary Vasculature Circ. Res., September 17, 1999; 85(6): 489 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matsuda, K. G. Morgan, and F. W. Sellke PRECONDITIONING IMPROVES CARDIOPLEGIA-RELATED CORONARY MICROVASCULAR SMOOTH MUSCLE HYPERCONTRACTILITY: ROLE OF KATP CHANNELS J. Thorac. Cardiovasc. Surg., September 1, 1999; 118(3): 438 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matsuda, M. Tofukuji, K. G. Morgan, and F. W. Sellke Coronary microvascular protection with Mg2+: effects on intracellular calcium regulation and vascular function Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1124 - H1130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Wilson, M. Dipp, J. M. Thomas, C. Lad, A. Galione, and A. M. Evans ADP-ribosyl Cyclase and Cyclic ADP-ribose Hydrolase Act as a Redox Sensor. A PRIMARY ROLE FOR CYCLIC ADP-RIBOSE IN HYPOXIC PULMONARY VASOCONSTRICTION J. Biol. Chem., March 30, 2001; 276(14): 11180 - 11188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Waypa, N. S. Chandel, and P. T. Schumacker Model for Hypoxic Pulmonary Vasoconstriction Involving Mitochondrial Oxygen Sensing Circ. Res., June 22, 2001; 88(12): 1259 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dipp and A. M. Evans Cyclic ADP-Ribose Is the Primary Trigger for Hypoxic Pulmonary Vasoconstriction in the Rat Lung In Situ Circ. Res., July 6, 2001; 89(1): 77 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Ng and A. M. Gurney Store-Operated Channels Mediate Ca2+ Influx and Contraction in Rat Pulmonary Artery Circ. Res., November 9, 2001; 89(10): 923 - 929. [Abstract] [Full Text] [PDF]
|
|