{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:24:17Z","timestamp":1791055457245,"version":"4.1.0"},"reference-count":32,"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":[[2003,6]]},"abstract":"<jats:p>\n            Endothelin-1 (ET-1) is a potent vasoconstrictor. Its effect on arterial wave reflections and central pressure augmentation is unknown. We studied whether ET-1, in plasma concentrations present in disease, increases pulse wave velocity (PWV) and augmentation index (AIx) and therefore compromises cardiac output, and whether the ET-1 receptor blocker VML-588 (previously AXV-034343 and Ro 61\u20131790) prevents such effects. Nine healthy men received a 2-hour infusion with ET-1 (2.5 ng \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 min\n            <jats:sup>\u22121<\/jats:sup>\n            ) superimposed on vehicle or VML-588 (0.05, 0.20, or 0.40 mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            ) (randomized order). Arterial tonometry and pulse wave contour analysis were used to assess aortic PWV and central aortic pressures and impedance cardiography for cardiac output. ET-1 slightly increased mean arterial pressure and peripheral resistance but had no significant effect on systolic blood pressure and pulse pressure. PWV increased from 5.4\u00b10.2 to 5.7\u00b10.3 m\/s (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), AIx from 9.9\u00b13.3 to 17.2\u00b13.8 (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), central systolic blood pressure by 8.7\u00b11.7 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), and central pulse pressure by 5.1\u00b11.9 mm Hg (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). This was associated with a fall in cardiac output by \u224818% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). VML-588 caused a slight decrease in brachial mean arterial pressure, PWV, and AIx, and prevented the effects of ET-1 on central hemodynamics without a clear dose-response effect. In summary, ET-1 in plasma concentrations as found in renal failure and heart failure accelerates PWV, causes a disproportionate increase in central aortic systolic blood pressure and pulse pressure, and decreases cardiac output. These effects can be prevented with an ET-1 receptor blocker such as VML-588. This makes it worthwhile to focus on endothelin as a target to prevent ventricular hypertrophy and to maintain cardiac function in diseases associated with high ET-1.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000072982.70666.e8","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T05:39:36Z","timestamp":1052804376000},"page":"1253-1258","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["Effects of Endothelin-1 and Endothelin-1 Receptor Blockade on Cardiac Output, Aortic Pressure, and Pulse Wave Velocity in Humans"],"prefix":"10.1161","volume":"41","author":[{"given":"Tycho J.L.","family":"Vuurmans","sequence":"first","affiliation":[{"name":"From the Department of Nephrology and Hypertension, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boer","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology and Hypertension, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein A.","family":"Koomans","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology and Hypertension, University Medical Center Utrecht, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"F411","volume":"266","year":"1994","unstructured":"Schwartz Sorensen S, Madsen JK, Pedersen EB. Systemic and renal effect of intravenous infusion of endothelin-1 in healthy humans. Am J Physiol. 1994; 266: F411\u2013F418.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.4.620"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.101.2.142"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1992.tb01463.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.80.6.1921"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00219-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199816080-00001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.38.6.1456"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.93.10.1860"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)92631-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.ndt.a027833"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.85.2.1735147"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91504-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.36.1.62"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.80.6.2598428"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199816121-00033"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.2.168"},{"key":"e_1_3_2_18_2","first-page":"1110","volume":"293","year":"1997","unstructured":"Roux S, Breu V, Giller T, Neidhart W, Ramuz H, Coassolo P, Clozel JP, Clozel M. Ro 61\u20131790, a new hydrosoluble endothelin antagonist: general pharmacology and effects on experimental cerebral vasospasm. J Exp Pharmacol Ther. 1997; 293: 1110\u20131118.","journal-title":"J Exp Pharmacol Ther"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199800001-00044"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70066-4"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200018030-00006"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.9.2131"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00296-9"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.5.491"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41966-7"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704304"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/92.10.595"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02252-X"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.13.1387"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.32.2.356"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00240-5"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(02)00182-1"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.0000072982.70666.E8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:44:41Z","timestamp":1715532281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.0000072982.70666.E8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1161\/01.HYP.0000072982.70666.E8"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.0000072982.70666.e8","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6]]},"assertion":[{"value":"2003-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}