(Hypertension. 1999;33:414-418.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of Tyrosine Kinase and PKC in the Vasoconstrictor Response to 20-HETE in Renal Arterioles
From the Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee; and the Department of Molecular Genetics (J.R.F.), University of Texas Southwestern Medical Center, Dallas.
Correspondence to Dr Richard J. Roman, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail rroman{at}post.its.mcw.edu
Abstract—The present study examined the hypothesis that activation of protein kinase C (PKC), components of the mitogen-activated protein (MAP) kinase pathway, or both contributes to the inhibitory effects of 20-hydroxyeicosatetraenoic acid (20-HETE) on K+-channel activity and its vasoconstrictor response in renal arterioles. 20-HETE (0.1 to 50 µmol/L) dose-dependently produced a 30% increase in PKC activity and a fivefold rise in the expression of active extracellular signal-regulated kinase 1 (ERK1) and ERK2 proteins in renal microvessels. 20-HETE (0.01 to 1 µmol/L) reduced the diameter of isolated perfused renal interlobular arterioles by 33±2%. Blockade of PKC activity with an N-myristoylated PKC pseudosubstrate inhibitor (Myr-PKCi, 100 µmol/L) or calphostin C (0.5 µmol/L) had no significant effect on the vasoconstrictor response to 20-HETE. In contrast, the tyrosine kinase inhibitors genistein (30 µmol/L) and tyrphostin 25 (10 µmol/L) reduced the response to 20-HETE by 76.5±2.1% and 67.5±1.8%, respectively. A specific inhibitor of mitogen-activated extracellular signal-regulated kinase (MEK), PD98059, had no effect on the vasoconstrictor response to 20-HETE. In cell-attached patches on renal vascular smooth muscle cells, 20-HETE reduced the open state probability of a large-conductance K+ channel (from 0.0026±0.0004 to 0.0006±0.0001). The Myr-PKCi (100 µmol/L) did not alter the inhibitory effects of 20-HETE on this channel. In contrast, the tyrosine kinase inhibitor genistein (30 µmol/L) blocked the inhibitory effects of 20-HETE on the large-conductance K+ channel. These data suggest that 20-HETE activates the MAP kinase system in renal arterioles and that the activation of a tyrosine kinase, which is proximal to MEK in this cascade, contributes to the inhibitory effects of 20-HETE on K+-channel activity and its vasoconstrictor effects in the renal arterioles.
Key Words: kinase • muscle, smooth, vascular • arachidonic acid • renal circulation • cytochrome P450 • potassium channels
This article has been cited by other articles:
 |
|
 |
|
  T. Akbulut, K. R. Regner, R. J. Roman, E. D. Avner, J. R. Falck, and F. Park 20-HETE activates the Raf/MEK/ERK pathway in renal epithelial cells through an EGFR- and c-Src-dependent mechanism Am J Physiol Renal Physiol, September 1, 2009; 297(3): F662 - F670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sugimoto, H. Akasaka, T. Katsuya, K. Node, T. Fujisawa, I. Shimaoka, O. Yasuda, M. Ohishi, T. Ogihara, K. Shimamoto, et al. A Polymorphism Regulates CYP4A11 Transcriptional Activity and Is Associated With Hypertension in a Japanese Population Hypertension, December 1, 2008; 52(6): 1142 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Guo, J. Sheng, G. M. Scicli, A. S. Arbab, N. L. Lehman, P. A. Edwards, J. R. Falck, R. J. Roman, and A. G. Scicli Expression of CYP4A1 in U251 Human Glioma Cell Induces Hyperproliferative Phenotype in Vitro and Rapidly Growing Tumors in Vivo J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 10 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cheng, J.-S. Ou, H. Singh, J. R. Falck, D. Narsimhaswamy, K. A. Pritchard Jr., and M. L. Schwartzman 20-Hydroxyeicosatetraenoic acid causes endothelial dysfunction via eNOS uncoupling Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1018 - H1026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-J. Liang, H. E. Ives, C.-M. Yang, and Y.-H. Ma 20-HETE inhibits the proliferation of vascular smooth muscle cells via transforming growth factor- J. Lipid Res., January 1, 2008; 49(1): 66 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Williams, M. Sharma, S. Anjaiahh, J. R. Falck, and R. J. Roman Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier Am J Physiol Renal Physiol, August 1, 2007; 293(2): F501 - F505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Wang, H. Singh, F. Zhang, T. Ishizuka, H. Deng, R. Kemp, M. S. Wolin, T. H. Hintze, N. G. Abraham, A. Nasjletti, et al. Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus Circ. Res., April 14, 2006; 98(7): 962 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Guo, R. J. Roman, J. R. Falck, P. A. Edwards, and A. G. Scicli Human U251 Glioma Cell Proliferation Is Suppressed by HET0016 [N-Hydroxy-N'-(4-butyl-2-methylphenyl)formamidine], a Selective Inhibitor of CYP4A J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 526 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takeuchi, M. Renic, Q. C. Bohman, D. R. Harder, N. Miyata, and R. J. Roman Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2203 - H2211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. H. Collins, S. D. Harmon, T. L. Kaduce, K. B. Berst, X. Fang, S. A. Moore, T. V. Raju, J. R. Falck, N. L. Weintraub, G. Duester, et al. {omega}-Oxidation of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in Cerebral Microvascular Smooth Muscle and Endothelium by Alcohol Dehydrogenase 4 J. Biol. Chem., September 30, 2005; 280(39): 33157 - 33164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Miyata, T. Seki, Y. Tanaka, T. Omura, K. Taniguchi, M. Doi, K. Bandou, S. Kametani, M. Sato, S. Okuyama, et al. Beneficial Effects of a New 20-Hydroxyeicosatetraenoic Acid Synthesis Inhibitor, TS-011 [N-(3-Chloro-4-morpholin-4-yl) Phenyl-N'-hydroxyimido Formamide], on Hemorrhagic and Ischemic Stroke J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 77 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Ljubimov and M. B. Grant P450 in the Angiogenesis Affair: The Unusual Suspect Am. J. Pathol., February 1, 2005; 166(2): 341 - 344. [Full Text] [PDF]
|
|
|
|
|
|
P. Chen, M. Guo, D. Wygle, P. A. Edwards, J. R. Falck, R. J. Roman, and A. G. Scicli Inhibitors of Cytochrome P450 4A Suppress Angiogenic Responses Am. J. Pathol., February 1, 2005; 166(2): 615 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Wang, F. Zhang, M. Jiang, M.-H. Wang, B. A. Zand, N. G. Abraham, A. Nasjletti, and M. Laniado-Schwartzman Transfection and Functional Expression of CYP4A1 and CYP4A2 Using Bicistronic Vectors in Vascular Cells and Tissues J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 913 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fuloria, D. M. Eckman, D. A. Leach, and J. L. Aschner 20-Hydroxyeicosatetraenoic acid is a vasoconstrictor in the newborn piglet pulmonary microcirculation Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L360 - L365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-I. Kaide, F. Zhang, Y. Wei, W. Wang, V. R. Gopal, J. R. Falck, M. Laniado-Schwartzman, and A. Nasjletti Vascular CO Counterbalances the Sensitizing Influence of 20-HETE on Agonist-Induced Vasoconstriction Hypertension, August 1, 2004; 44(2): 210 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Kaduce, X. Fang, S. D. Harmon, C. L. Oltman, K. C. Dellsperger, L. M. Teesch, V. R. Gopal, J. R. Falck, W. B. Campbell, N. L. Weintraub, et al. 20-Hydroxyeicosatetraenoic Acid (20-HETE) Metabolism in Coronary Endothelial Cells J. Biol. Chem., January 23, 2004; 279(4): 2648 - 2656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cavarape, N. Endlich, R. Assaloni, E. Bartoli, M. Steinhausen, N. Parekh, and K. Endlich Rho-Kinase Inhibition Blunts Renal Vasoconstriction Induced by Distinct Signaling Pathways In Vivo J. Am. Soc. Nephrol., January 1, 2003; 14(1): 37 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-I. Kaide, M.-H. Wang, J.-S. Wang, F. Zhang, V.R. Gopal, J. R. Falck, A. Nasjletti, and M. Laniado-Schwartzman Transfection of CYP4A1 cDNA increases vascular reactivity in renal interlobar arteries Am J Physiol Renal Physiol, January 1, 2003; 284(1): F51 - F56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alonso-Galicia, K. G. Maier, A. S. Greene, A. W. Cowley Jr., and R. J. Roman Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R60 - R68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Zhang, M.-H. Wang, U.M. Krishna, J. R. Falck, M. Laniado-Schwartzman, and A. Nasjletti Modulation by 20-HETE of Phenylephrine-Induced Mesenteric Artery Contraction in Spontaneously Hypertensive and Wistar-Kyoto Rats Hypertension, December 1, 2001; 38(6): 1311 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhao, E. W. Inscho, M. Bondlela, J. R. Falck, and J. D. Imig The CYP450 hydroxylase pathway contributes to P2X receptor-mediated afferent arteriolar vasoconstriction Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2089 - H2096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-M. Gu, Y. Wei, J. R. Falck, U. M. Krishna, and W.-H. Wang Effects of protein tyrosine kinase and protein tyrosine phosphatase on apical K+ channels in the TAL Am J Physiol Cell Physiol, October 1, 2001; 281(4): C1188 - C1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Kunert, R. J. Roman, M. Alonso-Galicia, J. R. Falck, and J. H. Lombard Cytochrome P-450 {omega}-hydroxylase: a potential O2 sensor in rat arterioles and skeletal muscle cells Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1840 - H1845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Parmentier, M. M. Muthalif, A. T. Nishimoto, and K. U. Malik 20-Hydroxyeicosatetraenoic Acid Mediates Angiotensin II-Induced Phospholipase D Activation in Vascular Smooth Muscle Cells Hypertension, February 1, 2001; 37(2): 623 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Jacobs and D. C. Zeldin The lung HETEs (and EETs) up Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H1 - H10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Imig Eicosanoid regulation of the renal vasculature Am J Physiol Renal Physiol, December 1, 2000; 279(6): F965 - F981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Carroll and J. C McGiff A new class of lipid mediators: cytochrome P450 arachidonate metabolites Thorax, October 1, 2000; 55(90002): 13S - 16. [Full Text]
|
|
|
|
|
|
M. Alonso-Galicia, J. R. Falck, K. M. Reddy, and R. J. Roman 20-HETE agonists and antagonists in the renal circulation Am J Physiol Renal Physiol, November 1, 1999; 277(5): F790 - F796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. McGiff and J. Quilley 20-HETE and the kidney: resolution of old problems and new beginnings Am J Physiol Regulatory Integrative Comp Physiol, September 1, 1999; 277(3): R607 - R623. [Abstract] [Full Text] [PDF]
|
|