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Brain expression of VEGF and its receptors in SHR-SP and effects of an endothelin blocker.

Abstract：

:Spontaneously hypertensive stroke-prone rats suffer spontaneous strokes partly as a result of abnormal cerebrovascular development. This model exhibits prehypertensive, typical hypertensive and malignant hypertensive stages. We had observed that vascular endothelial growth factor and its receptors, kinase domain region (KDR) and fms-like tyrosine kinase (Flt-1), were upregulated in the frontal cortex of spontaneously hypertensive stroke-prone rats at the typical hypertensive stage. The current study therefore investigated whether the long-term treatment with an endothelin-A/endothelin-B dual receptor antagonist, SB209670, or saline (vehicle) starting at the prehypertensive stage (6 weeks old) could reverse the upregulated vascular endothelial growth factor and its receptors; this upregulation is believed to be a compensatory adaptation for hypertension in the brain of spontaneously hypertensive stroke-prone rats. A 40% upregulation of vascular endothelial growth factor was observed in the brain of vehicle-treated spontaneously hypertensive stroke-prone rats compared with the age-matched genetic control, Wistar-Kyoto rat, and this upregulation was markedly reversed by endothelin antagonism. A similar change was found in KDR and Flt-1 expression. It is worth noting that the vascular endothelial growth factor/KDR signaling system was upregulated in the brain of spontaneously hypertensive stroke-prone rats treated with vehicle at the typical hypertensive stage, whereas the cerebral blood flow did not differ between Wistar-Kyoto and spontaneously hypertensive stroke-prone rats. We concluded that endothelin antagonism reversed the upregulated vascular endothelial growth factor and its receptors in the frontal cortex of spontaneously hypertensive stroke-prone rats at the typical hypertensive stage, and it is suggested that endothelin antagonism can reverse the hypertension-induced neurovascular remodeling in the brain of these rats.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Jesmin S,Sakuma I,Togashi H,Yoshioka M,Hattori Y,Kitabatake A,Miyauchi T

doi

10.1097/01.fjc.0000166264.27476.60

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

S160-4

eissn

0160-2446

issn

1533-4023

pii

00005344-200411001-00042

journal_volume

44 Suppl 1

pub_type

杂志文章

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Brain expression of VEGF and its receptors in SHR-SP and effects of an endothelin blocker.