THE ANGIOTENSIN AT(1) RECEPTOR ANTAGONIST CV-11974 REGULATES CEREBRALBLOOD-FLOW AND BRAIN ANGIOTENSIN AT(1) RECEPTOR EXPRESSION

Citation
Y. Nishimura et al., THE ANGIOTENSIN AT(1) RECEPTOR ANTAGONIST CV-11974 REGULATES CEREBRALBLOOD-FLOW AND BRAIN ANGIOTENSIN AT(1) RECEPTOR EXPRESSION, Basic research in cardiology, 93, 1998, pp. 63-68
Citations number
14
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiac & Cardiovascular System
ISSN journal
0300-8428
Volume
93
Year of publication
1998
Supplement
2
Pages
63 - 68
Database
ISI
SICI code
0300-8428(1998)93:<63:TAARAC>2.0.ZU;2-0
Abstract
We studied cerebral blood flow autoregulation by laser Doppler flowmet ry, and expression of brain angiotensin II AT(1) receptors by quantita tive autoradiography, after administration of an angiotensin AT(1) rec eptor antagonist, CV-11974 (Candesartan, 0.5 or 1.0 mg/kg day) for two weeks via subcutaneously implanted osmotic pumps in adult normotensiv e Wistar Kyoto and spontaneously hypertensive male rats (SHR). In SHR, the autoregulation curve was shifted towards higher blood pressures, when compared with that of normotensive Wistar Kyoto rats. Administrat ion of CV-11974 shifted the autoregulation curve toward lower blood pr essures in both Wistar Kyoto and SHR, partially normalizing the autore gulation curve in SHR. CV-11974 treatment markedly decreased the expre ssion of AT, receptors in Wistar Kyoto rats, both in areas outside the blood brain barrier (subfornical organ, 95 % decrease) and inside the blood brain barrier (nucleus of the tractus solitarius, 87 % decrease , and paraventricular nucleus, 96 % decrease). Our results demonstrate that blockade of AT(1) receptors tends to normalize the shift to high er pressures in the autoregulation curve:of genetically hypertensive r ats, and has a profound modulatory role in brain angiotensin II AT(1) receptors.