title: Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage.
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.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ueno
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D000367:Age Factors; D000818:Animals; D001783:Blood Flow Velocity; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D015536:Down-Regulation; D019332:Endothelin-1 / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D020521:Stroke / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B