{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:08:09Z","timestamp":1762160889830,"version":"3.38.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:p><jats:italic>Background and Purpose<\/jats:italic>\u2014While it has been widely reported that the vasospasm following subarachnoid hemorrhage (SAH) is prevented\/reversed by endothelin (ET) receptor antagonists selective for the ET<jats:sub>A<\/jats:sub>receptor and by nonselective ET receptor antagonists, ie, antagonists of both the ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub>receptors, there are no reports on the possible attenuation of the spasm by selective ET<jats:sub>B<\/jats:sub>receptor antagonists. The purpose of this study was to investigate whether (1) ET<jats:sub>B<\/jats:sub>receptor antagonists prevent and reverse SAH-induced spasm and (2) attenuation of the spasm results from blockade of smooth muscle ET<jats:sub>B<\/jats:sub>(ET<jats:sub>B2<\/jats:sub>) receptor\u2013mediated constriction and\/or endothelial ET<jats:sub>B<\/jats:sub>(ET<jats:sub>B1<\/jats:sub>) receptor\u2013 mediated ET-1\u2013induced ET-1 release.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>\u2014SAH-induced spasm of the rabbit basilar artery was induced with the use of a double hemorrhage model. In vivo effects of agents on the spasm were determined by angiography after their intracisternal infusion (10 \u03bcL\/h) by mini osmotic pump. In situ effects of agents on the spasm were determined by direct measurement of vessel diameter after their suffusion in a cranial window.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>\u2014SAH constricted the basilar artery by 30%. Intracisternal infusion with 10 \u03bcmol\/L BQ788, an ET<jats:sub>B1\/B2<\/jats:sub>receptor antagonist, reduced the spasm to 10%. To investigate whether BQ788 prevented the spasm by blockade of ET<jats:sub>B1<\/jats:sub>receptor\u2013mediated ET-1\u2013induced ET-1 release, as opposed to ET<jats:sub>B2<\/jats:sub>receptor\u2013mediated constriction, we tested whether ET<jats:sub>B1<\/jats:sub>receptor blockade also prevented the spasm. Indeed, intracisternal infusion with 10 \u03bcmol\/L RES-701-1, a selective ET<jats:sub>B1<\/jats:sub>receptor antagonist, reduced the spasm to 10%. Similarly, in situ superfusion with 1 \u03bcmol\/L BQ788 reversed the spasm by 40%, and 1 \u03bcmol\/L RES-701-1 reversed the spasm by 50%. However, both BQ788 and RES-701-1 enhanced by 40% to 50% the 3 nmol\/L ET-1\u2013induced constriction elicited in spastic vessels previously relaxed with 0.1 mmol\/L phosphoramidon, an ET-converting enzyme inhibitor.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014These results demonstrate that ET<jats:sub>B<\/jats:sub>receptor antagonists prevent and reverse SAH-induced cerebral vasospasm in an animal model. The likely mechanism underlying the attenuation of the spasm is blockade of ET<jats:sub>B1<\/jats:sub>receptor\u2013mediated ET-1\u2013induced ET-1 release of newly synthesized ET-1. These studies provide rationale for the therapeutic use of ET<jats:sub>B1<\/jats:sub>receptor antagonists to relieve the vasospasm following SAH, as well as other pathophysiological conditions involving possible ET-1\u2013induced ET-1 release.<\/jats:p>","DOI":"10.1161\/01.str.29.9.1924","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"1924-1929","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Endothelin B Receptor Antagonists Attenuate Subarachnoid Hemorrhage\u2013Induced Cerebral Vasospasm"],"prefix":"10.1161","volume":"29","author":[{"given":"Mario","family":"Zuccarello","sequence":"first","affiliation":[{"name":"From the Departments of Neurosurgery (M.Z., R.B., A.R.) and Pharmacology and Cell Biophysics (R.B., R.M.R.), University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Boccaletti","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (M.Z., R.B., A.R.) and Pharmacology and Cell Biophysics (R.B., R.M.R.), University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Romano","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (M.Z., R.B., A.R.) and Pharmacology and Cell Biophysics (R.B., R.M.R.), University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"Rapoport","sequence":"additional","affiliation":[{"name":"From the Departments of Neurosurgery (M.Z., R.B., A.R.) and Pharmacology and Cell Biophysics (R.B., R.M.R.), University of Cincinnati College of Medicine, and Veterans Affairs Medical Center, Cincinnati, Ohio."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2139"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90007-P"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1994.81.5.0759"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.25.12.7974589"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1995.83.3.0503"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00070-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199507000-00012"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-199507000-00013"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.9.1629"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1996.84.3.0503"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/S0022-3565(24)37130-7","volume":"283","year":"1997","unstructured":"Roux S, Breu V, Giller T, Neidhart W, Ramuz H, Coassolo P, Clozel JP, Clozel M. 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