{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:29:11Z","timestamp":1762079351997,"version":"3.40.3"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1995,6]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>Endothelin is a potent pressor agent mediated primarily through activation of endothelin-A receptors on vascular smooth muscle. Surprisingly, there is no consensus in the literature regarding the role of endothelin itself or endothelin-A receptors in hypertension. The goal of this study was to compare the effects of the novel, selective endothelin-A receptor antagonist BMS-182874 in various models of hypertension. BMS-182874 specifically inhibited the pressor response to endothelin-1 (0.3 nmol\/kg IV) in Sprague-Dawley rats in a dose-dependent manner (ED<jats:sub>25<\/jats:sub>=8 \u03bcmol\/kg IV) but had no effect on changes in mean arterial pressure brought about by other vasoactive agents. The antihypertensive effects of BMS-182874 were evaluated in conscious deoxycorticosterone acetate (DOCA)\u2013salt hypertensive rats, spontaneously hypertensive rats (SHR), and sodium-deplete SHR. BMS-182874 reduced blood pressure in DOCA-salt hypertensive rats when administered at a dose of 30, 100, or 300 \u03bcmol\/kg IV. A maximal decrease of approximately 45 mm Hg was observed after treatment with 100 \u03bcmol\/kg IV. Three days of oral or intravenous treatment with BMS-182874 (100 \u03bcmol\/kg) elicited a sustained decrease in blood pressure in the DOCA-salt hypertensive rats. In SHR, BMS-182874 decreased blood pressure by approximately 30 mm Hg, but the antihypertensive effects were similar at doses of 75, 150, and 450 \u03bcmol\/kg PO. In sodium-deplete SHR, BMS-182874 did not significantly reduce blood pressure. In summary, BMS-182874 is a specific, orally active endothelin-A receptor antagonist that is efficacious in mineralocorticoid hypertension in rats but has less effect in sodium-replete and sodium-deplete SHR. Thus, endothelin-A receptor activation may play a role in volume-dependent or low-renin hypertension but is unlikely to be important in all hypertensive states.<\/jats:p>","DOI":"10.1161\/01.hyp.25.6.1191","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:24:03Z","timestamp":1339460643000},"page":"1191-1195","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Antihypertensive Effects of a Novel Endothelin-A Receptor Antagonist in Rats"],"prefix":"10.1161","volume":"25","author":[{"given":"J. Eileen","family":"Bird","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Moreland","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas L.","family":"Waldron","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Powell","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90736-4"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90424-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.6.747"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.6.752"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.3.294"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.6.916"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.24.2.183"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00029a001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/6.8.667"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(91)90155-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0022-3565(25)24736-X","volume":"257","year":"1991","unstructured":"Tomobe Y, Ishikawa T, Yanagisawa M, Kimura S, Masaki T, Goto K. Mechanisms of altered sensitivity to endothelin-1 between aortic smooth muscles of spontaneously hypertensive and Wistar-Kyoto rats. J Pharmacol Exp Ther. 1991;257:555-561.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/S0022-3565(25)24538-4","volume":"272","year":"1995","unstructured":"Webb ML, Bird JE, Liu ECK, Rose PM, Serafino R, Stein PD, Moreland S. BMS-182874 is a selective, nonpeptide endothelin ETA receptor antagonist. J Pharmacol Exp Ther. 1995;272:1124-1134.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-104-25937"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_3_2_15_2","first-page":"H1782","volume":"262","year":"1992","unstructured":"Deng LW, Schiffrin EL. Effects of endothelin on resistance arteries of DOCA-salt hypertensive rats. 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