RRC ID 90
Author Jesmin S, Sakuma I, Togashi H, Yoshioka M, Hattori Y, Kitabatake A, Miyauchi T.
Title Brain expression of VEGF and its receptors in SHR-SP and effects of an endothelin blocker.
Journal J. Cardiovasc. Pharmacol.
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.
Volume 44 Suppl 1
Pages S160-4
Published 2004-11
PII 00005344-200411001-00042
PMID 15838270
MeSH Age Factors Animals Antihypertensive Agents / pharmacology* Cerebral Cortex / drug effects* Cerebral Cortex / metabolism Disease Models, Animal Endothelin Receptor Antagonists* Hypertension / complications Hypertension / drug therapy* Hypertension / metabolism Indans / pharmacology* Male Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Endothelin / metabolism Stroke / drug therapy Stroke / etiology Stroke / metabolism Up-Regulation Vascular Endothelial Growth Factor A / metabolism* Vascular Endothelial Growth Factor Receptor-1 / metabolism* Vascular Endothelial Growth Factor Receptor-2 / metabolism*
IF 2.371
Times Cited 2
WOS Category CARDIAC & CARDIOVASCULAR SYSTEMS PHARMACOLOGY & PHARMACY
Resource
Rats WKY/Ezo(strainID=568) SHRSP/Ezo(strainID=357)