Hypoxia‑induced 15‑HETE enhances the constriction of internal carotid arteries by down‑regulating potassium channels

Written by Yanmei Zhu, Li Chen, Wenjuan Liu, Weizhi Wang, Daling Zhu, Yulan Zhu

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Severe hypoxia induces the constriction of internal carotid arteries (ICA), which worsens ischemic stroke in the brain. A few metabolites are presumably involved in hypoxic vasoconstriction, however, less is known about how such molecules provoke this vasoconstriction. We have investigated the influence of 15‑hydroxyeicosatetrienoic acid (15‑HETE) produced by 15‑lipoxygenase (15‑LOX) on vasoconstriction during hypoxia. As showed in our results, 15‑LOX level increases in ICA endothelia and smooth muscles. 15‑HETE enhances the tension of ICA ring in a dose‑dependent manner, as well as attenuates the activity and expression of voltage‑gated potassium (Kv) channels. Therefore, the down‑regulation of Kv channels by 15‑HETE during hypoxia weakens the repolarization of action potentials and causes a dominant influx of calcium to enhance smooth muscle tension and ICA constriction.

Ссылки на авторов:

Yanmei Zhu, Li Chen, Wenjuan Liu, Weizhi Wang, Yulan Zhu
Second Affiliated Hospital of Harbin Medical University
Daling Zhu
College of Pharmacy of Harbin Medical University (157 Baojian Road, Nangang District, Harbin 150081 P.R. China)

  1. Aoki K., Zubkov A.Y., Parent A.D. [et al.] Mechanism of ATP‑induced [Ca2+] imobilization in rat basilar smooth muscle cell // Stroke. 2000. Vol. 31. P. 1377–1384.
  2. Archer S., Michelakis E. The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O(2) sensors, and controversies // News Physiol. Sci. 2002. Vol. 17. P. 131–137.
  3. Badimon L., Vilahur G. Platelets, arterial thrombosis and cerebral ischemia // Cerebrovasc. Dis. 2007. Vol. 24, Suppl. 1. P. 30–39.
  4. Chung Y.H., Kim H.S., Shin C.M. [et al.] Immunohistochemical study on the distribution of voltage‑gated K+ channels in rat brain following transient focal ischemia // Neuroscience Letters. 2001. Vol. 308, No. 3. P. 157–160.
  5. Elizabeth A.C., Michael M.T. Differential expression of KV channel α and β subunits in the bovine pulmonary arterial circulation // Am. J. Physiol. Lung Cell. Mol. Physiol. 2001. Vol. 281. P. L1350– L1360.
  6. Fu Z.J., Xie M.J., Zhang L.F. [et al.] Differential activation of potassium channels in cerebral and hindquarter arteries of rats during stimulated microgravity // Am. J. Physiol. Heart. Circ. Physiol. 2004. Vol. 287, No. 4. P. 1505–1515.
  7. Gregory C.A., Luis F.S. Kv2 channels oppose myogenic constriction of rat cerebral arteries // Am. J. Physiol. Cell. Physiol. 2006. Vol. 291, No. 2. P. C348–C356.
  8. Harm J.K., Mark T.N. Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure // J. Physiol. 1998. Vol. 508. P. 199–209.
  9. Lopez‑Barneo J., Lopez‑Lopez J.R., Urena J., Gonzalez C. Chemotransduction in the carotid body: K+ current modulated by PO2 in type‑chemoreceptor cells // Science. 1988. Vol. 241 (4865). P. 580–582.
  10. Siesjö B.K. Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment // J. Neurosurg. 1992. Vol. 77, No. 3. P. 337–354.
  11. Standen N.B., Quayle J.M. K+ channel modulation in arterial smooth muscle // Acta Physiol. Scand. 1998. Vol. 164, No. 4. P. 549–557.
  12. Uski T.K., Hogestatt E.D. Effects of various cyclooxygenase and lipoxygenase metabolites on guinea‑pig cerebral arteries // Gen. Pharmacol. 1992. Vol. 23, No. 1. P. 109–113.
  13. Zhu D., Medhora M., Campbell W.B. [et al.] Chronic hypoxia activates lung 15‑lipoxygenase, which catalyzes production of 15‑HETE and enhances constriction in neonatal rabbit pulmonary arteries // Circ. Res. 2003. Vol. 92, No. 9. P. 992–1000.
  14. Zhu Y., Shan H., Li Q., Zhu D. Contractile effect and mechanism of 15‑HETE on hypoxic rat internal carotid arteries rings // Chinese Pharmacological Bulletin. 2005. Vol. 21, No. 11. P. 1327–1332.
  15. Zhu Yu‑Lan, Su Fang, Chan He, Zhu Da‑1ing. Expression and location of 15‑lipoxygenase in hypoxic rat brain // Journal of Clinical Rehabilitative Tissue Engineering Research. 2005. Vol. 9, No. 1. P. 90–92.


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