AJP - Heart Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 279: H1616-H1624, 2000;
0363-6135/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (41)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bhardwaj, A.
Right arrow Articles by Koehler, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhardwaj, A.
Right arrow Articles by Koehler, R. C.
Vol. 279, Issue 4, H1616-H1624, October 2000

P-450 epoxygenase and NO synthase inhibitors reduce cerebral blood flow response to N-methyl-D-aspartate

Anish Bhardwaj1,2, Frances J. Northington3, Juan R. Carhuapoma1,2, John R. Falck4, David R. Harder5, Richard J. Traystman2, and Raymond C. Koehler2

1 Departments of Neurology, 2 Anesthesiology and Critical Care Medicine, and 3 Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; 4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390; and 5 Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Epoxyeicosatrienoic acids are cerebral vasodilators produced in astrocytes by cytochrome P-450 epoxygenase activity. The P-450 inhibitor miconazole attenuates the increase in cerebral blood flow (CBF) elicited by glutamate. We evaluated whether epoxygenase activity is involved in the CBF response to activation of the N-methyl-D-aspartate (NMDA) receptor subtype by using two structurally distinct inhibitors, miconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH), a selective epoxygenase substrate inhibitor. Drugs were delivered locally through microdialysis probes in striata of anesthetized rats. Local CBF was measured by hydrogen clearance and compared with CBF in contralateral striatum receiving vehicle. Microdialysis perfusion of NMDA doubled CBF and increased nitric oxide (NO) production estimated by recovery of labeled citrulline in the dialysate during labeled arginine infusion. Perfusion of miconazole or MS-PPOH blocked the increase in CBF without decreasing citrulline recovery. Perfusion of Nomega -nitro-L-arginine decreased baseline CBF and inhibited the CBF response to NMDA. Perfusion of MS-PPOH did not inhibit the CBF response to sodium nitroprusside. We conclude that both the P-450 epoxygenase and NO synthase pathways are involved in the local CBF response to NMDA receptor activation, and that the signaling pathway may be more complex than simply NO diffusion from neurons to vascular smooth muscle.

arachidonic acid; epoxyeicosatrienoic acid; glia; miconazole; microdialysis; nitric oxide; rat


This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
N. Toda, K. Ayajiki, and T. Okamura
Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances
Pharmacol. Rev., March 1, 2009; 61(1): 62 - 97.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
V. M. Blanco, J. E. Stern, and J. A. Filosa
Tone-dependent vascular responses to astrocyte-derived signals
Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2855 - H2863.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. Li, Q. Xi, E. S. Umstot, L. Bellner, M. L. Schwartzman, J. H. Jaggar, and C. W. Leffler
Astrocyte-Derived CO Is a Diffusible Messenger That Mediates Glutamate-Induced Cerebral Arteriolar Dilation by Activating Smooth Muscle Cell KCa Channels
Circ. Res., February 1, 2008; 102(2): 234 - 241.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
H. Ohata, S. Cao, and R. C. Koehler
Contribution of adenosine A2A and A2B receptors and heme oxygenase to AMPA-induced dilation of pial arterioles in rats
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R728 - R735.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. Ayata and M. A. Moskowitz
Cortical spreading depression confounds concentration-dependent pial arteriolar dilation during N-methyl-D-aspartate superfusion
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1837 - H1841.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
R. C. Koehler, D. Gebremedhin, and D. R. Harder
Role of astrocytes in cerebrovascular regulation
J Appl Physiol, January 1, 2006; 100(1): 307 - 317.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. J. Iliff, R. D'Ambrosio, A. C. Ngai, and H. R. Winn
Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex
Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1631 - H1637.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
X. Peng, J. R. Carhuapoma, A. Bhardwaj, N. J. Alkayed, J. R. Falck, D. R. Harder, R. J. Traystman, and R. C. Koehler
Suppression of cortical functional hyperemia to vibrissal stimulation in the rat by epoxygenase inhibitors
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2029 - H2037.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
T. Horiuchi, H. H. Dietrich, K. Hongo, T. Goto, and R. G. Dacey Jr
Role of Endothelial Nitric Oxide and Smooth Muscle Potassium Channels in Cerebral Arteriolar Dilation in Response to Acidosis
Stroke, March 1, 2002; 33(3): 844 - 849.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
D. R. Harder, C. Zhang, and D. Gebremedhin
Astrocytes Function in Matching Blood Flow to Metabolic Activity
Physiology, February 1, 2002; 17(1): 27 - 31.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
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]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Dai and J. H. Zhang
Role of Cl- current in endothelin-1-induced contraction in rabbit basilar artery
Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2159 - H2167.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
F. Domoki, J. V. Perciaccante, K. Shimizu, M. Puskar, D. W. Busija, and F. Bari
N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets
Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1404 - H1409.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online