Remote limb ischemic preconditioning attenuates cerebrovascular depression during sinusoidal galvanic vestibular stimulation via α1-adrenoceptor-protein kinase Cε-endothelial no synthase pathway in rats

Devin W. McBride, Cesar Reis, John H. Zhang, Richard Lee Applegate, Jiping Tang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background--Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. Methods and Results--We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. Conclusions--Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor- protein kinase Ce-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

Original languageEnglish (US)
Article numbere007105
JournalJournal of the American Heart Association
Volume7
Issue number7
DOIs
StatePublished - Apr 1 2018
Externally publishedYes

Fingerprint

Ischemic Preconditioning
Cerebrovascular Circulation
Vasovagal Syncope
Adrenergic Receptors
Protein Kinase C
Extremities
Depression
Nitric Oxide Synthase Type III
Norepinephrine Plasma Membrane Transport Proteins
Bradycardia
Controlled Hypotension
Brain
Syncope
Hypotension
Protein Kinases
Norepinephrine
Arterial Pressure
Perfusion
Heart Rate
Wounds and Injuries

Keywords

  • Catecholamine
  • Ischemia
  • Preconditioning
  • Syncope

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{89e235ab7acd4f7db8fc75064bf55836,
title = "Remote limb ischemic preconditioning attenuates cerebrovascular depression during sinusoidal galvanic vestibular stimulation via α1-adrenoceptor-protein kinase Cε-endothelial no synthase pathway in rats",
abstract = "Background--Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. Methods and Results--We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. Conclusions--Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor- protein kinase Ce-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.",
keywords = "Catecholamine, Ischemia, Preconditioning, Syncope",
author = "McBride, {Devin W.} and Cesar Reis and Zhang, {John H.} and Applegate, {Richard Lee} and Jiping Tang",
year = "2018",
month = "4",
day = "1",
doi = "10.1161/JAHA.117.007105",
language = "English (US)",
volume = "7",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Remote limb ischemic preconditioning attenuates cerebrovascular depression during sinusoidal galvanic vestibular stimulation via α1-adrenoceptor-protein kinase Cε-endothelial no synthase pathway in rats

AU - McBride, Devin W.

AU - Reis, Cesar

AU - Zhang, John H.

AU - Applegate, Richard Lee

AU - Tang, Jiping

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background--Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. Methods and Results--We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. Conclusions--Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor- protein kinase Ce-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

AB - Background--Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. Methods and Results--We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. Conclusions--Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor- protein kinase Ce-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

KW - Catecholamine

KW - Ischemia

KW - Preconditioning

KW - Syncope

UR - http://www.scopus.com/inward/record.url?scp=85044872007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044872007&partnerID=8YFLogxK

U2 - 10.1161/JAHA.117.007105

DO - 10.1161/JAHA.117.007105

M3 - Article

C2 - 29574462

AN - SCOPUS:85044872007

VL - 7

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 7

M1 - e007105

ER -