20-Hydroxyeicosatetraenoic Acid Potentiates Contractile Activation of Canine Basilar Artery in Response to Stretch Via Protein Kinase Cα- Mediated Inhibition of Calcium- Activated Potassium Channel

  • Koichi Nakayama
  • Kazuo Obara
  • Yoshiyuki Tanabe
  • Tomohisa Ishikawa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 538)


Blood vessels are persistently exposed to hemodynamic forces in the form of pressure and flow. The vascular smooth muscle contracts in response to stretch/increased intraluminal pressure, and dilates in response to release/decreased intraluminal pressure (Bayliss, 1902). This autoregulatory response is myogenic in nature, and is called “Bayliss effect.” To the contrary, flow/shear stress-dependent dilatation, so called “Schrezenmayar effect” (1933), caused by released vasodilators including nitric oxide from vascular endothelium or other components, can physiologically counteract the myogenic contraction. The cerebral artery is particularly sensitive to pressure and stretch, and shows myogenic contraction (Nakayama et al., 2002). Furthermore, we previously reported that large conductance Ca2+-activated K+ channel (KCa channel) blockers, including iberiotoxin, charybdotoxin, and tetraethylammonium, sensitized the canine basilar artery to mechanical stretch (Obara et al., 2001).


Cytochrome P450 Monooxygenase Epoxyeicosatrienoic Acid Vascular Smooth Muscle Contract Coronary Artery Smooth Muscle Cell Canine Basilar Artery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Bayliss, W.M., 1902, On the local reaction of the arterial wall to change of internal pressure. J. Physiol, 28: 220–231.PubMedGoogle Scholar
  2. Campbell, W.B., Gebremedhin, D., Pratt, P.F., and Harder, D.R., 1996, Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res., 78: 415–423.PubMedCrossRefGoogle Scholar
  3. Hansson, A., Serhan, C.N., Haeggstrom, J., Ingekma-Sundberg, M., and Samuelsson, B., 1986, Activation of protein kinase C by lipoxin A and other eicosanoids. Intracellular action of oxygenation products of arachidonic acid. Biochem. Biophys. Res. Commun., 134: 1215–1222.PubMedCrossRefGoogle Scholar
  4. Harder, D.R., Gebremedhin, D., Narayanan, J., Jefcoat, C, Falck, J.R., Campbell, W.B., and Roman, R., 1994, Formation and action of a P-450 4A metabolite of arachidonic acid in cat cerebral microvessels. Am. J. Physiol, 266: H2098–H2107.PubMedGoogle Scholar
  5. Lange, A., Gebremedhin, D., Narayanan, J., and Harder, D., 1997, 20-Hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J. Biol. Chem., 272:27345–27352.PubMedCrossRefGoogle Scholar
  6. Ma, Y.H., Gebremedhin, D., Schwartzman, ML., Falck, J.R., Clark, J.E., Masters, B.S., Harder, D.R., and Roman, R.J., 1993, 20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries. Circ. Res., 72: 126–136.PubMedCrossRefGoogle Scholar
  7. Minami, K., Fukuzawa, K., and Nakaya, Y., 1993, Protein kinase C inhibits the Ca2+-activated K+ channel of cultured porcine coronary artery smooth muscle cells. Biochem. Biophys. Res. Commun., 190:263–269.PubMedCrossRefGoogle Scholar
  8. Murakami, K., Chan, S.Y., and Routtenberg, A, 1986, Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids. J. Biol Chem., 261:15424–15429.PubMedGoogle Scholar
  9. Nakayama, K., 1982, Calcium-dependent contractile activation of cerebral artery produced by quick stretch. Am. J. Physiol, 242: H760–H768.PubMedGoogle Scholar
  10. Nakayama, K., Obara, K.,Tanabe, Y., Saito, M., Ishikawa, T., and Nishizawa, S., 2002, Interactive role of tyrosine kinase, protein kinase C, and Rho/Rho kinase systems in the mechanotransduction of vascular smooth muscles. Biorheology, in press.Google Scholar
  11. Nishizawa, S., Obara, K., Nakayama, K., Koide, M., Yokoyama, T., Yokota, N., and Ohta, S., 2000, Protein kinase Cd and a are involved in the development of vasospasm after subarachnoid hemorrhage. Eur. J. Pharmacol., 398:113–119.PubMedCrossRefGoogle Scholar
  12. Obara, K., Koide, M., and Nakayama, K., 2002, 20-Hydroxyeicosatetraenoic acid potentiates stretch-inudced contraction of canine basilar artery via PKCα-mediated inhibition of Kc_ channel. Br. J. Pharmacol., inpress.Google Scholar
  13. Obara, K., Saito, M., Yamanaka, A., Uchino, M., and Nakayama, K., 2001, Involvement of different activator Ca2+ in the rate-dependent stretch-induced contractions of canine basilar artery. Jpn. J. Physiol., 51: 327–335.PubMedCrossRefGoogle Scholar
  14. Ribalet, B., and Eddlestone, G.T., 1995, Characterization of the G protein coupling of SRIF and beta-adrenergic receptors to the maxi Kca channel in insulin-secreting cells. J. Membr. Biol, 148:111–125.PubMedGoogle Scholar
  15. Schrezenmayar, A., 1933, Über regulatorisch Vorgange an Muskelarterien. Pflügers. Arch. 232:743–748.CrossRefGoogle Scholar
  16. Sekiguchi, K., Tsukuda, M., Ogita, K., Kikkawa, U., and Nishizuka, Y., 1987, Three distinct forms of rat brain protein kinase C: differential response to unsaturated fatty acids. Biochem. Biophys. Res. Commun., 145: 797–802.PubMedCrossRefGoogle Scholar
  17. Shipston, M.J., and Armstrong, D.L., 1996, Activation of protein kinase C inhibits calcium-activated potassium channels in rat pituitary tumour cells. J. Physiol. (Lond.), 493:665–672.Google Scholar
  18. Walsh, MP., Andrea, J.E., Allen, B.G., Clement-Chomiennep, O., Cpllins, E.M, and Morgan, K.G., 1994, Smooth muscle protein kinase C. Can. J. Physiol. Pharmacol, 72: 1392–1399.PubMedCrossRefGoogle Scholar
  19. Zhang, H., Weir, B., and Daniel, E.E., 1995, Activation of protein kinase C inhibits potassium currents in cultured endothelial cells. Pharmacology, 50: 247–256.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Koichi Nakayama
    • 1
  • Kazuo Obara
    • 1
  • Yoshiyuki Tanabe
    • 1
  • Tomohisa Ishikawa
    • 1
  1. 1.Department of PharmacologySchool of Pharmaceutical Sciences, University of ShizuokaShizuokaJapan

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