Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage.
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.
Jesmin
Subrina
S
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sakuma
Ichiro
I
Togashi
Hiroko
H
Yamaguchi
Taku
T
Ueno
Ken-ichi
K
Yoshioka
Mitsuhiro
M
Hattori
Yuichi
Y
Kitabatake
Akira
A
Miyauchi
Takashi
T
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
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B