Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1-induced peroxynitrite generation

Marilyn J. Cipolla; Julie G. Sweet; Natalia I. Gokina; Sheryl L. White; Mark T. Nelson

doi:10.1038/jcbfm.2013.99

Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1-induced peroxynitrite generation

Marilyn J. Cipolla, Julie G. Sweet, Natalia I. Gokina, Sheryl L. White, Mark T. Nelson

Research output: Contribution to journal › Article › peer-review

Abstract

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 (ET B) 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, Ca 2+-sensitive K + channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ET B agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L; P

Original language	English
Pages (from-to)	1486-1492
Number of pages	6
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	33
Issue number	10
DOIs	https://doi.org/10.1038/jcbfm.2013.99
Publication status	Published - Oct 2013

Keywords

EDH
endothelin-1
focal ischemia
parenchymal arterioles
peroxynitrite

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10.1038/jcbfm.2013.99

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title = "Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1-induced peroxynitrite generation",

abstract = "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 (ET B) 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, Ca 2+-sensitive K + channels (apamin and TRAM-34, respectively) were significantly enhanced in PAs from tMCAO compared with pMCAO or sham. Addition of the ET B agonist sarafotoxin caused constriction in PAs from tMCAO but not from sham animals (21±4% versus 3±3% at 1 nmol/L; P",

keywords = "EDH, endothelin-1, focal ischemia, parenchymal arterioles, peroxynitrite",

author = "Cipolla, {Marilyn J.} and Sweet, {Julie G.} and Gokina, {Natalia I.} and White, {Sheryl L.} and Nelson, {Mark T.}",

note = "P01 HL095488, NHLBI NIH HHS, United StatesR01 NS045940, NINDS NIH HHS, United States",

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Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1-induced peroxynitrite generation. / Cipolla, Marilyn J.; Sweet, Julie G.; Gokina, Natalia I. et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 33, No. 10, 10.2013, p. 1486-1492.

Research output: Contribution to journal › Article › peer-review

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AU - White, Sheryl L.

AU - Nelson, Mark T.

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ER -

Mechanisms of enhanced basal tone of brain parenchymal arterioles during early postischemic reperfusion: Role of ET-1-induced peroxynitrite generation

Abstract

Keywords

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