Document Detail


Isolated human and rat cerebral arteries constrict to increases in flow: role of 20-HETE and TP receptors.
MedLine Citation:
PMID:  21610722     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevation of intraluminal pressure increases vasomotor tone, which thought to have a substantial role in regulation of cerebral blood flow (CBF). Interestingly, responses of cerebral vessels to increases in flow varied and have not been studied in human cerebral arteries. We hypothesized that increases in flow elicit constrictions of isolated human and rat cerebral arteries and aimed to elucidate the underlying mechanisms. Human cerebral arteries and rat middle cerebral arteries constricted to increases in flow (P<0.05). Simultaneous increase in intraluminal flow+pressure further reduced the diameter compared with pressure-induced changes (P<0.05), leading to constant estimated CBF. Flow-induced constrictions were abolished by HET0016 (inhibitor of synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) or inhibition of COXs or blocking TP (thromboxane A(2)/prostaglandin H(2), receptors and attenuated by scavenging reactive oxygen species (ROS). Flow-enhanced ROS formation was significantly reduced by HET0016. In conclusion, in human and rat cerebral arteries (1) increases in flow elicit constrictions, (2) signaling mechanism of flow-induced constriction of cerebral arteries involves enhanced production of ROS, COX activity, and mediated by 20-HETE via TP receptors, and (3) we propose that simultaneous operation of pressure- and flow-induced constrictions is necessary to provide an effective autoregulation of CBF.
Authors:
Peter Toth; Bernadett Rozsa; Zsolt Springo; Tamas Doczi; Akos Koller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-25
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  31     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2011-11-18     Revised Date:  2011-11-30    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2096-105     Citation Subset:  IM    
Affiliation:
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Blood Flow Velocity
Blood Pressure*
Female
Humans
Hydroxyeicosatetraenoic Acids / metabolism,  pharmacology*
Male
Middle Cerebral Artery / metabolism*,  physiology*
Organ Culture Techniques
Rats
Rats, Inbred WKY
Reactive Oxygen Species / metabolism
Receptors, Thromboxane A2, Prostaglandin H2 / metabolism*
Signal Transduction / drug effects,  physiology
Vasoconstriction / drug effects*
Grant Support
ID/Acronym/Agency:
P0-1 HL-43023/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; 0/Reactive Oxygen Species; 0/Receptors, Thromboxane A2, Prostaglandin H2; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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