| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Physiologisches Institut, Ludwig Maximilians Universität, München, Germany; and
* Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universität, Frankfurt, Germany
1Correspondence: Physiologisches Institut, Ludwig Maximilians Universität, Schillerstrasse 44, D-80336 München. E-mail: bolz{at}lrz.uni-muenchen.de
Using a novel vessel culture technique in combination with antisense oligonucleotide transfection, we tested whether the endothelium-derived hyperpolarizing factor (EDHF) is a cytochrome P450 (CYP)-related compound. Isolated resistance arteries from hamster gracilis muscle (n=19) were perfused and exposed to antisense (As), sense (S), or scrambled (Scr) oligonucleotides against the coding region of CYP2C8/9, an isoform expressed in endothelial cells. Thereafter, NO- and prostaglandin-independent, EDHF-mediated vascular responses associated with hyperpolarization [i.e., decrease in smooth muscle calcium (Fura 2) and vasodilation] were studied after the application of acetylcholine (ACh). These EDHF-mediated responses were markedly attenuated (by 70%) by As- but not by S- or Scr-oligonucleotide treatment. However, the responses to norepinephrine (0.3 µmol/l), the NO donor sodium nitroprusside (1 µmol/l), and the KCa channel activator NS1619 (100 µmol/l) were unaltered. As treatment, which specifically targeted the endothelial layer (as assessed by confocal microscopy), had no inhibitory effect on increases in endothelial calcium to ACh. It is concluded that a CYP2C8/9-related isoform functions as an EDHF synthase in hamster resistance arteries and that a product of this enzyme is an EDHF, or at least an integral part of the signaling cascade leading to EDHF-mediated responses.—Bolz, S.-S., Fisslthaler, B., Pieperhoff, S., de Wit, C., Fleming, I., Busse, R., Pohl, U. Antisense oligonucleotides against cytochrome P450 2C8 attenuate EDHF-mediated Ca2+ changes and dilation in isolated resistance arteries.
Key Words: organ culture • cytochrome P450 metabolites • hyperpolarization • endothelium • acetylcholine
This article has been cited by other articles:
|
|
 |
|
  J. Wray and D. Bishop-Bailey Epoxygenases and peroxisome proliferator-activated receptors in mammalian vascular biology Exp Physiol, January 1, 2008; 93(1): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Mortensen, J. Gonzalez-Alonso, R. Damsgaard, B. Saltin, and Y. Hellsten Inhibition of nitric oxide and prostaglandins, but not endothelial-derived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg J. Physiol., June 1, 2007; 581(2): 853 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Hagedorn, C.-L. Cooke, J. R. Falck, B. F. Mitchell, and S. T. Davidge Regulation of Vascular Tone During Pregnancy: A Novel Role for the Pregnane X Receptor Hypertension, February 1, 2007; 49(2): 328 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lu, D. Ye, X. Wang, J. M. Seubert, J. P. Graves, J. A. Bradbury, D. C. Zeldin, and H.-C. Lee Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms J. Physiol., September 1, 2006; 575(2): 627 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Taddei, D. Versari, A. Cipriano, L. Ghiadoni, F. Galetta, F. Franzoni, A. Magagna, A. Virdis, and A. Salvetti Identification of a Cytochrome P450 2C9-Derived Endothelium-Derived Hyperpolarizing Factor in Essential Hypertensive Patients J. Am. Coll. Cardiol., August 1, 2006; 48(3): 508 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Feletou and P. M. Vanhoutte Endothelium-Derived Hyperpolarizing Factor: Where Are We Now? Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1215 - 1225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Siegl, M. Koeppen, S. E. Wolfle, U. Pohl, and C. de Wit Myoendothelial Coupling Is Not Prominent in Arterioles Within the Mouse Cremaster Microcirculation In Vivo Circ. Res., October 14, 2005; 97(8): 781 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Watanabe, J. Suzuki, H. Yamawaki, V. K. Sharma, S.-S. Sheu, and B. C. Berk Losartan Metabolite EXP3179 Activates Akt and Endothelial Nitric Oxide Synthase via Vascular Endothelial Growth Factor Receptor-2 in Endothelial Cells: Angiotensin II Type 1 Receptor-Independent Effects of EXP3179 Circulation, September 20, 2005; 112(12): 1798 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. You, E. M. Golding, and R. M. Bryan Jr. Arachidonic acid metabolites, hydrogen peroxide, and EDHF in cerebral arteries Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1077 - H1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, X. Wei, X. Xiao, R. Hui, J. W. Card, M. A. Carey, D. W. Wang, and D. C. Zeldin Arachidonic Acid Epoxygenase Metabolites Stimulate Endothelial Cell Growth and Angiogenesis via Mitogen-Activated Protein Kinase and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 522 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koeppen, R. Feil, D. Siegl, S. Feil, F. Hofmann, U. Pohl, and C. de Wit cGMP-Dependent Protein Kinase Mediates NO- but not Acetylcholine-Induced Dilations in Resistance Vessels In Vivo Hypertension, December 1, 2004; 44(6): 952 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Clifford and Y. Hellsten Vasodilatory mechanisms in contracting skeletal muscle J Appl Physiol, July 1, 2004; 97(1): 393 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Bolz, L. Vogel, D. Sollinger, R. Derwand, C. de Wit, G. Loirand, and U. Pohl Nitric Oxide-Induced Decrease in Calcium Sensitivity of Resistance Arteries Is Attributable to Activation of the Myosin Light Chain Phosphatase and Antagonized by the RhoA/Rho Kinase Pathway Circulation, June 24, 2003; 107(24): 3081 - 3087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Earley, A. Pastuszyn, and B. R. Walker Cytochrome P-450 epoxygenase products contribute to attenuated vasoconstriction after chronic hypoxia Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H127 - H136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Krotz, H. Y. Sohn, M. Keller, T. Gloe, S. S. Bolz, B. F. Becker, and U. Pohl Depolarization of Endothelial Cells Enhances Platelet Aggregation Through Oxidative Inactivation of Endothelial NTPDase Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2003 - 2009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hoepfl, B. Rodenwaldt, U. Pohl, and C. de Wit EDHF, but not NO or prostaglandins, is critical to evoke a conducted dilation upon ACh in hamster arterioles Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H996 - H1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bauersachs, M. Christ, G. Ertl, U.R. Michaelis, B. Fisslthaler, R. Busse, and I. Fleming Cytochrome P450 2C expression and EDHF-mediated relaxation in porcine coronary arteries is increased by cortisol Cardiovasc Res, June 1, 2002; 54(3): 669 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Golding, S. P. Marrelli, J. You, and R. M. Bryan Jr Endothelium-Derived Hyperpolarizing Factor in the Brain: A New Regulator of Cerebral Blood Flow? Stroke, March 1, 2002; 33(3): 661 - 663. [Full Text] [PDF]
|
|
|
|
|
|
L. A. Schildmeyer and R. M. Bryan Jr. Effect of NO on EDHF response in rat middle cerebral arteries Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H734 - H738. [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]
|
|
|
|
 |
|
 B. C. BERK, J.-I. ABE, W. MIN, J. SURAPISITCHAT, and C. YAN Endothelial Atheroprotective and Anti-inflammatory Mechanisms Ann. N.Y. Acad. Sci., December 1, 2001; 947(1): 93 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Fleming Cytochrome P450 and Vascular Homeostasis Circ. Res., October 26, 2001; 89(9): 753 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Tuttle and J. C. Falcone Nitric oxide release during {alpha}1-adrenoceptor-mediated constriction of arterioles Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H873 - H881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Coats, F. Johnston, J. MacDonald, J. J. V. McMurray, and C. Hillier Endothelium-Derived Hyperpolarizing Factor : Identification and Mechanisms of Action in Human Subcutaneous Resistance Arteries Circulation, March 27, 2001; 103(12): 1702 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Fleming, U. R. Michaelis, D. Bredenkötter, B. Fisslthaler, F. Dehghani, R. P. Brandes, and R. Busse Endothelium-Derived Hyperpolarizing Factor Synthase (Cytochrome P450 2C9) Is a Functionally Significant Source of Reactive Oxygen Species in Coronary Arteries Circ. Res., January 19, 2001; 88(1): 44 - 51. [Abstract] [Full Text]
|
|
|
|
|
|
S.-S. Bolz, J. Galle, R. Derwand, C. de Wit, and U. Pohl Oxidized LDL Increases the Sensitivity of the Contractile Apparatus in Isolated Resistance Arteries for Ca2+ via a Rho- and Rho Kinase-Dependent Mechanism Circulation, November 7, 2000; 102(19): 2402 - 2410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Bolz, S. Pieperhoff, C. De Wit, and U. Pohl Intact endothelial and smooth muscle function in small resistance arteries after 48 h in vessel culture Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1434 - H1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Popp, R. P. Brandes, G. Ott, R. Busse, and I. Fleming Dynamic Modulation of Interendothelial Gap Junctional Communication by 11,12-Epoxyeicosatrienoic Acid Circ. Res., April 19, 2002; 90(7): 800 - 806. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
