Expression of endothelin receptors in the brain of SHR-SP and effects of an endothelin blocker.
Increased levels of endothelin-1 have been demonstrated in the ischemic brain, and endothelin receptor antagonism has been shown to improve the outcome of cerebral ischemia. However, it remains unknown what the relative receptor distribution in the brain of the spontaneously hypertensive stroke-prone rat (SHR-SP) is and whether it is changed by endothelin antagonism. The present study aimed to investigate the expression of the two endothelin receptors in the frontal cortex of SHR-SP after 12 weeks of treatment with an endothelin-A/endothelin-B dual receptor antagonist, SB209670, or saline (vehicle) starting from the prehypertensive stage (6 weeks old). A 50% increase in the endothelin-A receptor was found in the vehicle-treated brain of SHR-SP compared with that of the age-matched Wistar-Kyoto control, but endothelin antagonism reversed this upregulation completely. A 20% decrease in endothelin-B receptor was found in the vehicle-treated brain of SHR-SP compared with Wistar-Kyoto and was recovered by endothelin antagonism. This is the first study to explore the relative endothelin receptor distribution in the frontal cortex of SHR-SP at the typical hypertensive stage and changes resulting from long-term endothelin antagonism starting from the prehypertensive stage.
Jesmin
Subrina
S
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sakuma
Ichiro
I
Togashi
Hiroko
H
Yoshioka
Mitsuhiro
M
Hattori
Yuichi
Y
Kitabatake
Akira
A
Miyauchi
Takashi
T
D000367:Age Factors; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; 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 / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D007189:Indans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-