Author Jesmin S, Sakuma I, Togashi H, Yamaguchi T, Ueno K, Yoshioka M, Hattori Y, Kitabatake A, Miyauchi T.
Title Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage.
Journal 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.
Volume 44 Suppl 1
Pages S11-5
Published 2004-11
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 2.371
Times Cited 3
Rats WKY/Ezo(strainID=568) SHRSP/Ezo(strainID=357)