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Requirement of Pretone by Thromboxane $A_2$ for Hypoxic Pulmonary Vasoconstriction in Precision-cut Lung Slices of Rat

  • Park, Su-Jung (Department of Physiology, Seoul National University College of Medicine) ;
  • Yoo, Hae-Young (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Hye-Jin (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Jin-Kyoung (Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Zhang, Yin-Hua (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Sung-Joon (Department of Physiology, Seoul National University College of Medicine)
  • Received : 2012.01.10
  • Accepted : 2012.01.25
  • Published : 2012.02.29

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, $K^+$ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the $K^+$ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine ($EC_{50}$, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholineinduced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

Keywords

References

  1. Bonnet S, Dubuis E, Vandier C, Martin S, Marthan R, Savineau JP. Reversal of chronic hypoxia-induced alterations in pulmonary artery smooth muscle electromechanical coupling upon air breathing. Cardiovasc Res. 2002;53:1019-1028. https://doi.org/10.1016/S0008-6363(01)00548-X
  2. Osipenko ON, Alexander D, MacLean MR, Gurney AM. Influence of chronic hypoxia on the contributions of non-inactivating and delayed rectifier K currents to the resting potential and tone of rat pulmonary artery smooth muscle. Br J Pharmacol. 1998;124:1335-1337. https://doi.org/10.1038/sj.bjp.0702006
  3. Yoo HY, Park SJ, Seo EY, Park KS, Han JA, Kim KS, Shin DH, Earm YE, Zhang YH, Kim SJ. Role of thromboxane A2-activated nonselective cation channels in hypoxic pulmonary vasoconstriction of rat. Am J Physiol Cell Physiol. 2012; 302:C307-317. https://doi.org/10.1152/ajpcell.00153.2011
  4. Leach RM, Robertson TP, Twort CH, Ward JP. Hypoxic vasoconstriction in rat pulmonary and mesenteric arteries. Am J Physiol. 1994;266:L223-231.
  5. Rodman DM, Yamaguchi T, O'Brien RF, McMurtry IF. Hypoxic contraction of isolated rat pulmonary artery. J Pharmacol Exp Ther. 1989;248:952-959.
  6. Park SJ, Yoo HY, Earm YE, Kim SJ, Kim JK, Kim SD. Role of arachidonic acid-derived metabolites in the control of pulmonary arterial pressure and hypoxic pulmonary vasoconstriction in rats. Br J Anaesth. 2011;106:31-37. https://doi.org/10.1093/bja/aeq268
  7. Sanderson MJ. Exploring lung physiology in health and disease with lung slices. Pulm Pharmacol Ther. 2011;24:452-465. https://doi.org/10.1016/j.pupt.2011.05.001
  8. Struckmann N, Schwering S, Wiegand S, Gschnell A, Yamada M, Kummer W, Wess J, Haberberger RV. Role of muscarinic receptor subtypes in the constriction of peripheral airways: studies on receptor-deficient mice. Mol Pharmacol. 2003;64:1444-1451. https://doi.org/10.1124/mol.64.6.1444
  9. Moreno L, Perez-Vizcaino F, Harrington L, Faro R, Sturton G, Barnes PJ, Mitchell JA. Pharmacology of airways and vessels in lung slices in situ: role of endogenous dilator hormones. Respir Res. 2006;7:111. https://doi.org/10.1186/1465-9921-7-111
  10. Paddenberg R, Konig P, Faulhammer P, Goldenberg A, Pfeil U, Kummer W. Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices. Respir Res. 2006;7:93. https://doi.org/10.1186/1465-9921-7-93
  11. Bai Y, Sanderson MJ. Modulation of the Ca^{2+}$ sensitivity of airway smooth muscle cells in murine lung slices. Am J Physiol Lung Cell Mol Physiol. 2006;291:L208-221. https://doi.org/10.1152/ajplung.00494.2005
  12. Martin C, Uhlig S, Ullrich V. Cytokine-induced bronchoconstriction in precision-cut lung slices is dependent upon cyclooxygenase-2 and thromboxane receptor activation. Am J Respir Cell Mol Biol. 2001;24:139-145. https://doi.org/10.1165/ajrcmb.24.2.3545
  13. Bergner A, Sanderson MJ. Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices. J Gen Physiol. 2002;119:187-198. https://doi.org/10.1085/jgp.119.2.187
  14. Brueggemann LI, Kakad PP, Love RB, Solway J, Dowell ML, Cribbs LL, Byron KL. Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy. Am J Physiol Lung Cell Mol Physiol. 2012;302:L120-132. https://doi.org/10.1152/ajplung.00194.2011
  15. Ressmeyer AR, Larsson AK, Vollmer E, Dahlen SE, Uhlig S, Martin C. Characterisation of guinea pig precision-cut lung slices: comparison with human tissues. Eur Respir J. 2006;28:603-611. https://doi.org/10.1183/09031936.06.00004206
  16. Desireddi JR, Farrow KN, Marks JD, Waypa GB, Schumacker PT. Hypoxia increases ROS signaling and cytosolic $Ca^{2+}$ in pulmonary artery smooth muscle cells of mouse lungs slices. Antioxid Redox Signal. 2010;12:595-602. https://doi.org/10.1089/ars.2009.2862
  17. Held HD, Martin C, Uhlig S. Characterization of airway and vascular responses in murine lungs. Br J Pharmacol. 1999;126:1191-1199. https://doi.org/10.1038/sj.bjp.0702394
  18. Martin C, Uhlig S, Ullrich V. Videomicroscopy of methacholineinduced contraction of individual airways in precision-cut lung slices. Eur Respir J. 1996;9:2479-2487. https://doi.org/10.1183/09031936.96.09122479
  19. Wetzel RC, Herold CJ, Zerhouni EA, Robotham JL. Hypoxic bronchodilation. J Appl Physiol. 1992;73:1202-1206.

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