Mechanisms of Enhanced Basal Tone of Brain Parenchymal Arterioles During Early Postischemic Reperfusion: Role of ET-1-Induced Peroxynitrite Generation

The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hour...

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Published in:Journal of cerebral blood flow and metabolism 2013-10, Vol.33 (10), p.1486-1492
Main Authors: Cipolla, Marilyn J, Sweet, Julie G, Gokina, Natalia I, White, Sheryl L, Nelson, Mark T
Format: Article
Language:English
Subjects:
Animals
Arterioles - drug effects
Arterioles - metabolism
Arterioles - physiopathology
Brain Ischemia - complications
Brain Ischemia - metabolism
Brain Ischemia - physiopathology
Cerebrovascular Circulation - physiology
Endothelin-1 - metabolism
Endothelium, Vascular - physiology
Male
Microcirculation - physiology
Muscle Tonus - physiology
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - physiopathology
Peroxynitrous Acid - metabolism
Rats
Rats, Wistar
Real-Time Polymerase Chain Reaction
Receptor, Endothelin B - metabolism
Reperfusion Injury - complications
Reperfusion Injury - metabolism
Reperfusion Injury - physiopathology
Vasodilation - physiology
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Summary:The contributions of vasoconstrictors (endothelin-1 (ET-1), peroxynitrite) and endothelium-dependent vasodilatory mechanisms to basal tone were investigated in parenchymal arterioles (PAs) after early postischemic reperfusion. Transient middle cerebral artery occlusion (tMCAO) was induced for 2 hours with 30 minutes reperfusion in male Wistar rats and compared with ischemia alone (permanent MCAO (pMCAO);2.5 hours) or sham controls. Changes in lumen diameter of isolated and pressurized PAs were compared. Quantitative PCR was used to measure endothelin type B (ETB) receptors. Constriction to intravascular pressure (‘basal tone’) was not affected by tMCAO or pMCAO. However, constriction to inhibitors of endothelial cell, small-(SK) and intermediate-(IK) conductance, Ca2+-sensitive K+ channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ETB agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L;P
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.2013.99