RRC ID |
92
|
著者 |
Jesmin S, Sakuma I, Togashi H, Yamaguchi T, Ueno K, Yoshioka M, Hattori Y, Kitabatake A, Miyauchi T.
|
タイトル |
Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage.
|
ジャーナル |
J Cardiovasc Pharmacol
|
Abstract |
Spontaneously hypertensive stroke-prone rats (SHR-SP) suffer spontaneous stroke in part as a result of abnormal cerebrovascular development. Reduction of regional cerebral blood flow in this model has already been demonstrated. This model has three distinct stages of hypertension: pre-hypertensive, typical hypertensive and malignant hypertensive. We investigated the level of endothelin-1 and its receptor expression in the frontal cortex of SHR-SP at the malignant hypertensive stage (35-40 weeks of age), during which time the rats suffer strokes. The cerebral endothelin-1 level, as determined by enzyme-linked immunosorbent assay, was highly increased at this severely hypertensive stage compared to their genetic control, normotensive Wistar-Kyoto rats. This upregulation was associated with an increased expression of endothelin-A receptor, however, another endothelin-1 receptor, endothelin-B, was downregulated. The regional cerebral blood flow in the frontal cortex was reduced by 60% in 40-week-old malignantly SHR-SP as compared to age-matched Wistar-Kyoto rats. Thus, cerebral endothelin-1 expression increased in malignant hypertension in SHR-SP. The enhanced endothelin-1 may activate the endothelin-A receptor, which would, in turn, result in reduced cerebral blood flow. Downregulation of the endothelin-B receptor may cause suppression of endothelium-derived relaxing factors in the brain of SHR-SP and be an underlying factor in their stroke susceptibility.
|
巻・号 |
44 Suppl 1
|
ページ |
S11-5
|
公開日 |
2004-11-1
|
DOI |
10.1097/01.fjc.0000166224.57970.91
|
PII |
00005344-200411001-00005
|
PMID |
15838256
|
MeSH |
Age Factors
Animals
Blood Flow Velocity
Cerebral Cortex / metabolism*
Cerebral Cortex / physiopathology
Cerebrovascular Circulation*
Disease Models, Animal
Down-Regulation
Endothelin-1 / metabolism*
Hypertension / complications
Hypertension / metabolism*
Hypertension / physiopathology
Male
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptor, Endothelin A / metabolism*
Receptor, Endothelin B / metabolism*
Stroke / etiology*
Stroke / metabolism
Stroke / physiopathology
Up-Regulation
|
IF |
2.598
|
引用数 |
4
|
WOS 分野
|
CARDIAC & CARDIOVASCULAR SYSTEMS
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ラット |
WKY/Ezo(strainID=568)
SHRSP/Ezo(strainID=357) |