{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:07:17Z","timestamp":1777396037061,"version":"3.51.4"},"reference-count":55,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T00:00:00Z","timestamp":1577923200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,2,4]]},"abstract":"<jats:p>\n                    Cerebral blood flow is reduced in Alzheimer\u2019s disease (AD), which is associated with mid-life hypertension. In people with increased cerebral vascular resistance due to vertebral artery or posterior communicating artery hypoplasia, there is evidence that hypertension develops as a protective mechanism to maintain cerebral perfusion. In AD, amyloid-\u03b2 (A\u03b2) accumulation may similarly raise cerebral vascular resistance by upregulation of the cerebral endothelin system. The level of endothelin-1 in brain tissue correlates positively with A\u03b2 load and negatively with markers of cerebral hypoperfusion such as increased vascular endothelial growth factor. We previously showed that cerebroventricular infusion of A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    exacerbated pre-existing hypertension in Dahl rats. We have investigated the effects of 28-day cerebral infusion of A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    on blood pressure and heart rate and their variability; carotid flow; endothelin-1; and markers of cerebral oxygenation, in the (normotensive) Wistar rat, and the modulatory influence of the endothelin A receptor antagonist Zibotentan (ZD4054). Cerebral infusion of A\u03b2 caused progressive rise in blood pressure ( p\u200a&lt;\u200a0.0001) (paired t-test: increase of 3 (0.1\u20135.6) mmHg ( p\u200a=\u200a0.040)), with evidence of reduced baroreflex responsiveness, and accumulation of A\u03b2 and elevated endothelin-1 in the vicinity of the infusion. Oral Zibotentan (3\u200amg\/kg\/d, administered for 31\u200ad) abrogated the effects of A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    infusion on baroreflex responsiveness and blood pressure, which declined, although without reduction in carotid blood flow, and Zibotentan caused uncoupling of the positive linear relationship between endothelin-1 and vascular endothelial growth factor, which as a sensor of tissue oxygenation would be expected to increase if there were hypoperfusion.\n                  <\/jats:p>","DOI":"10.3233\/jad-190630","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T12:23:11Z","timestamp":1579868591000},"page":"1185-1199","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Zibotentan, an Endothelin A Receptor Antagonist, Prevents Amyloid-\u03b2-Induced Hypertension and Maintains Cerebral Perfusion"],"prefix":"10.1177","volume":"73","author":[{"given":"Jennifer C.","family":"Palmer","sequence":"first","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah M.","family":"Tayler","sequence":"additional","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Dyer","sequence":"additional","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick G.","family":"Kehoe","sequence":"additional","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian F.R.","family":"Paton","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical & Health Sciences, University of Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth","family":"Love","sequence":"additional","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600570"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21475"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141467"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.11.023"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200001)47:1<93::AID-ANA15>3.0.CO;2-8"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-016-4450-z"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.027448"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.04.507"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx112"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130086"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.2174\/1567205010666131119234845"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24647"},{"key":"ref013","doi-asserted-by":"crossref","first-page":"e0195838","DOI":"10.1371\/journal.pone.0195838","volume":"13","author":"Lee 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