Faculty Collaboration Database

Endothelin rather than 20-HETE contributes to loss of pial arteriolar dilation during focal cerebral ischemia with and without polymeric hemoglobin transfusion. Am J Physiol Regul Integr Comp Physiol 2009 May;296(5):R1412-8

Date

03/06/2009

Pubmed ID

19261918

Pubmed Central ID

PMC2689832

DOI

10.1152/ajpregu.00003.2009

Scopus ID

2-s2.0-66149101990 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

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.

Author List

Cao S, Wang LC, Kwansa H, Roman RJ, Harder DR, Koehler RC

MESH terms used to index this publication - Major topics in bold

Amidines
Animals
Arterioles
Blood Substitutes
Blood Transfusion
Brain Ischemia
Endothelin A Receptor Antagonists
Endothelins
Hemoglobins
Hydroxyeicosatetraenoic Acids
Male
Models, Animal
Oligopeptides
Pia Mater
Polymers
Rats
Rats, Wistar
Regional Blood Flow
Vasodilation