Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Hypothermia Inhibits Endothelium-Independent Vascular Contractility via Rho-kinase Inhibition

  • Chung, Yoon Hee (Department of Anatomy, College of Medicine, Chung-Ang University) ;
  • Oh, Keon Woong (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Kim, Sung Tae (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Park, Eon Sub (Department of Pathology, College of Medicine, Chung-Ang University) ;
  • Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Yoon, Hyuk-Jun (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu) ;
  • Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung Ang University) ;
  • Jeong, Ji Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • La, Hyen-Oh (Department of Pharmacology, College of Pharmacy, The Catholic University of Korea)
  • Received : 2016.10.20
  • Accepted : 2016.12.27
  • Published : 2018.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

The present study was undertaken to investigate the influence of hypothermia on endothelium-independent vascular smooth muscle contractility and to determine the mechanism underlying the relaxation. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Hypothermia significantly inhibited fluoride-, thromboxane $A_{2-}$, phenylephrine-, and phorbol ester-induced vascular contractions regardless of endothelial nitric oxide synthesis, suggesting that another pathway had a direct effect on vascular smooth muscle. Hypothermia significantly inhibited the fluoride-induced increase in pMYPT1 level and phorbol ester-induced increase in pERK1/2 level, suggesting inhibition of Rho-kinase and MEK activity and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxing effect of moderate hypothermia on agonist-induced vascular contraction regardless of endothelial function involves inhibition of Rho-kinase and MEK activities.

Keywords

References

  1. Ajay, M., Gilani, A. U. and Mustafa, M. R. (2003) Effects of flavonoids on vascular smooth muscle of the isolated rat thoracic aorta. Life Sci. 74, 603-612. https://doi.org/10.1016/j.lfs.2003.06.039
  2. Akata, T. (2007) Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating $Ca^{2+}$ mobilization and/or myofilament $Ca^{2+}$ sensitivity in vascular smooth muscle cells. J. Anesth. 21, 232-242. https://doi.org/10.1007/s00540-006-0488-4
  3. Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y. and Kaibuchi, K. (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J. Biol. Chem. 271, 20246-20249. https://doi.org/10.1074/jbc.271.34.20246
  4. Appel, L. J., Brands, M. W., Daniels, S. R., Karanja, N., Elmer, P. J. and Sacks, F. M. (2006) Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension 47, 296-308. https://doi.org/10.1161/01.HYP.0000202568.01167.B6
  5. Brietz, A., Schuch, K. V., Wangorsch, G., Lorenz, K. and Dandekar, T. (2016) Analyzing ERK 1/2 signalling and targets. Mol. Biosyst. 12, 2436-2446. https://doi.org/10.1039/C6MB00255B
  6. Evora, P. R., Cable, D. G., Chua, Y. L., Rodrigues, A. J., Pearson, P. J. and Schaff, H. V. (2007) Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia. Cryobiology 54, 106-113. https://doi.org/10.1016/j.cryobiol.2006.12.002
  7. Ferland, D. J., Darios, E. S., Neubig, R. R., Sjogren, B., Truong, N., Torres, R., Dexheimer, T. S., Thompson, J. M. and Watts, S. W. (2016) Chemerin-induced arterial contraction is Gi- and calcium-dependent. Vascul. Pharmacol. 88, 30-41.
  8. Gallet, C., Blaie, S., Levy-Toledano, S. and Habib, A. (2003) Thromboxane-induced ERK phosphorylation in human aortic smooth muscle cells. Adv. Exp. Med. Biol. 525, 71-73.
  9. Goyal, R., Mittal, A., Chu, N., Shi, L., Zhang, L. and Longo L. D. (2009) Maturation and the role of PKC-mediated contractility in ovine cerebral arteries. Am. J. Physiol. Heart Circ. Physiol. 297, H2242-H2252. https://doi.org/10.1152/ajpheart.00681.2009
  10. Gu, Z., Kordowska, J., Williams, G. L., Wang, C. L. and Hai, C. M. (2007) Erk1/2 MAPK and caldesmon differentially regulate podosome dynamics in A7r5 vascular smooth muscle cells. Exp. Cell Res. 313, 849-866. https://doi.org/10.1016/j.yexcr.2006.12.005
  11. Ito, K., Matsuzaki, M., Sasahara, T., Shin, M. and Yayama, K. (2015) Orthovanadate-induced vasoconstriction of rat mesenteric arteries is mediated by rho kinase-dependent inhibition of myosin light chain phosphatase. Biol. Pharm. Bull. 38, 1809-1816. https://doi.org/10.1248/bpb.b15-00587
  12. Je, H. D. and Sohn, U. D. (2009) Inhibitory effect of genistein on agonist-induced modulation of vascular contractility. Mol. Cells 27, 191-198. https://doi.org/10.1007/s10059-009-0052-9
  13. Jensen, K. O., Held, L., Kraus, A., Hildebrand, F., Mommsen, P., Mica, L., Wanner, G. A., Steiger, P., Moos, R. M., Simmen, H. P. and Sprengel, K. (2016) The impact of mild induced hypothermia on the rate of transfusion and the mortality in severely injured patients: a retrospective multi-centre study. Eur. J. Med. Res. 21, 37. https://doi.org/10.1186/s40001-016-0233-x
  14. Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim, I. K. (2006) A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27-33. https://doi.org/10.1016/j.bbrc.2006.02.120
  15. Kim, J. G., Sung, H. J., Ok, S. H., Kwon, S. C., Cheon, K. S., Kim, H. J., Chang, K. C., Shin, I. W., Lee, H. K., Chung, Y. K. and Sohn, J. T. (2011) Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta. Can. J. Physiol. Pharmacol. 89, 681-689. https://doi.org/10.1139/y11-065
  16. Oh, T. G., Cha, W. C., Jo, I. J., Kang, M. J. and Lee, D. W. (2015) A survey-based study on the protocols for therapeutic hypothermia in cardiac arrest patients in Korea: focusing on the differences between level 1 and 2 centers. Clin. Exp. Emerg. Med. 2, 210-216. https://doi.org/10.15441/ceem.15.018
  17. Pfitzer, G. (2001) Invited review: regulation of myosin phosphorylation in smooth muscle. J. Appl. Physiol. 91, 497-503. https://doi.org/10.1152/jappl.2001.91.1.497
  18. Ruppert, C., Deiss, K., Herrmann, S., Vidal, M., Oezkur, M., Gorski, A., Weidemann, F., Lohse, M. J. and Lorenz, K. (2013) Interference with ERK(Thr188) phosphorylation impairs pathological but not physiological cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A. 110, 7440-7445. https://doi.org/10.1073/pnas.1221999110
  19. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. (2003) $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548-556.
  20. Somlyo, A. P. and Somlyo, A. V. (2003) $Ca^{2+}$ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 1325-1358. https://doi.org/10.1152/physrev.00023.2003
  21. Tankersley, C. G., Irizarry, R., Flanders, S. E., Rabold, R. and Frank, R. (2003) Unstable heart rate and temperature regulation predict mortality in AKR/J mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R742-R750. https://doi.org/10.1152/ajpregu.00416.2002
  22. Taubert, D., Berkels, R., Klaus, W. and Roesen, R. (2002) Nitric oxide formation and corresponding relaxation of porcine coronary arteries induced by plant phenols: essential structural features. J. Cardiovasc. Pharmacol. 40, 701-713. https://doi.org/10.1097/00005344-200211000-00008
  23. Tsai, M. H. and Jiang, M. J. (2006) Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction. Pflugers Arch. 453, 223-232. https://doi.org/10.1007/s00424-006-0133-y
  24. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990-994. https://doi.org/10.1038/40187
  25. Wier, W. G. and Morgan, K. G. (2003) ${\alpha}1$-Adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91-139.
  26. Wilson, D. P., Susnjar, M., Kiss, E., Sutherland, C. and Walsh, M. P. (2005) Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763-774.
  27. Wooldridge, A. A., MacDonald, J. A., Erdodi, F., Ma, C., Borman, M. A., Hartshorne, D. J. and Haystead, T. A. (2004) Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J. Biol. Chem. 279, 34496-34504. https://doi.org/10.1074/jbc.M405957200
  28. Zou, Q., Leung, S. W. and Vanhoutte, P. M. (2015) Transient receptor potential channel opening releases endogenous acetylcholine, which contributes to endothelium-dependent relaxation induced by mild hypothermia in spontaneously hypertensive rat but not wistar-kyoto rat arteries. J. Pharmacol. Exp. Ther. 354, 121-130. https://doi.org/10.1124/jpet.115.223693

Cited by

  1. Moderate hypothermia and responses to calcium channel blockers - Role of the nitric oxide vol.105, pp.1, 2018, https://doi.org/10.1556/2060.105.2018.1.2
  2. Moderate hypothermia and responses to calcium channel blockers - Role of the nitric oxide vol.105, pp.1, 2018, https://doi.org/10.1556/2060.105.2018.1.2