| Endothelin rather than 20-HETE contributes to loss of pial arteriolar dilation during focal cerebral ischemia with and without polymeric hemoglobin transfusion. | |
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MedLine Citation:
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PMID: 19261918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Partial exchange transfusion with a cell-free hemoglobin (Hb) polymer during transient middle cerebral artery occlusion (MCAO) reduces infarct volume but fails to increase blood flow, as might be expected with the induced decrease in hematocrit. In ischemic brain, endothelin antagonists are known to produce vasodilation. In nonischemic brain, pial arterioles constrict after Hb exchange transfusion, and the constriction is blocked by an inhibitor of 20-HETE synthesis. We tested the hypothesis that a 20-HETE synthesis inhibitor and an endothelin A receptor antagonist increase pial arteriolar dilation after Hb exchange transfusion during MCAO. Pial arteriolar diameter was measured in the ischemic border region of the distal MCA border region through closed cranial windows in anesthetized rats subjected to the filament model of MCAO. During 2 h of MCAO, pial arteriolar dilation gradually subsided from 37 +/- 3 to 7 +/- 5% (+/-SE). Compared with residual dilation at 2 h of MCAO with vehicle superfusion (14 +/- 3%), loss of dilation was not prevented by superfusion of a 20-HETE synthesis inhibitor (21 +/- 5%), partial Hb exchange transfusion (7 +/- 5%) that decreased hematocrit to 23%, or a combination of the two (5 +/- 5%). However, loss of dilation was prevented by superfusion of an endothelin A receptor antagonist with (35 +/- 4%) or without (32 +/- 5%) Hb transfusion. Pial artery constriction during reperfusion was attenuated by HET0016 alone and by BQ610 with or without Hb transfusion. Systemic administration of the endothelin antagonist during prolonged MCAO increased blood flow in the border region. Thus loss of pial arteriolar dilation in the ischemic border region during prolonged MCAO depends on endothelin A receptor activation, and this effect was independent of the presence of cell-free Hb polymers in the plasma. In contrast to previous work in nonischemic brain, inhibition of oxygen-dependent 20-HETE synthesis does not significantly influence the pial arteriolar response to polymeric Hb exchange transfusion during focal ischemia. |
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Authors:
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Suyi Cao; Liang-Chao Wang; Herman Kwansa; Richard J Roman; David R Harder; Raymond C Koehler |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-03-04 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 296 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-28 Completed Date: 2009-06-25 Revised Date: 2011-01-27 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R1412-8 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD 21287, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amidines
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pharmacology Animals Arterioles / drug effects, physiology* Blood Substitutes / administration & dosage, pharmacology Blood Transfusion Brain Ischemia / physiopathology* Endothelins / antagonists & inhibitors, physiology* Hemoglobins / administration & dosage, pharmacology* Hydroxyeicosatetraenoic Acids / antagonists & inhibitors, physiology* Male Models, Animal Oligopeptides / pharmacology Pia Mater / blood supply* Polymers Rats Rats, Wistar Receptor, Endothelin A / antagonists & inhibitors Regional Blood Flow / drug effects, physiology Vasodilation / drug effects, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL59996/HL/NHLBI NIH HHS; NS38684/NS/NINDS NIH HHS; R01 HL033833-26/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amidines; 0/Blood Substitutes; 0/Endothelins; 0/Hemoglobins; 0/Hydroxyeicosatetraenoic Acids; 0/N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine; 0/Oligopeptides; 0/Polymers; 0/Receptor, Endothelin A; 141595-53-1/BQ 610; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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