{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:20:58Z","timestamp":1793064058303,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,9,18]]},"abstract":"<jats:p><jats:bold><jats:italic><jats:italic>Background<\/jats:italic>\u2014<\/jats:italic><\/jats:bold>Angiotensin II is elevated in malignant hypertension. We tested the hypothesis that angiotensin II type 1 receptor blockade can prevent the development of malignant hypertension even in the absence of a blood pressure-lowering effect.<\/jats:p><jats:p><jats:bold><jats:italic><jats:italic>Methods and Results<\/jats:italic>\u2014<\/jats:italic><\/jats:bold>Two-kidney, 1-clip rats were followed up for 28 days; blood pressure was measured by tail-cuff plethysmography and intra-arterially. After a 2-week run-in phase, rats received valsartan at a dose of 0.3 (n=14) or 3 (n=12) mg \u00b7 kg<jats:sup>\u22121<\/jats:sup>\u00b7 d<jats:sup>\u22121<\/jats:sup>or solvent (n=27). Only the higher dose of valsartan, but not the lower dose, decreased blood pressure. Both doses of valsartan prevented the development of lethal malignant hypertension. Twenty of 27 solvent-treated renovascular hypertensive rats died, but only 3 of 14 rats treated with the low dose and 1 of 12 rats treated with the high dose of valsartan died. Histological signs of malignant nephrosclerosis were found in all rats examined that had died throughout the study and in 6 of 7 surviving solvent-treated renovascular hypertensive animals. Increased expression of monocyte chemoattractant protein-1 and prominent interstitial influx of macrophages occurred in the nonclipped kidneys exposed to high pressure in solvent-treated rats. These alterations were prevented by valsartan at both doses, irrespective of blood pressure effects.<\/jats:p><jats:p><jats:bold><jats:italic><jats:italic>Conclusions<\/jats:italic>\u2014<\/jats:italic><\/jats:bold>Angiotensin II type 1 receptor blockade by valsartan prevents lethal malignant hypertension independently of blood pressure. The results suggest that reduction of angiotensin-induced inflammation in the kidney may contribute to the protective effects of valsartan.<\/jats:p>","DOI":"10.1161\/hc3601.095576","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:31:09Z","timestamp":1191004269000},"page":"1436-1440","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension"],"prefix":"10.1161","volume":"104","author":[{"given":"Karl F.","family":"Hilgers","sequence":"first","affiliation":[{"name":"From the Department of Medicine IV, University of Erlangen, Nu\u0308rnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Hartner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine IV, University of Erlangen, Nu\u0308rnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Porst","sequence":"additional","affiliation":[{"name":"From the Department of Medicine IV, University of Erlangen, Nu\u0308rnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Veelken","sequence":"additional","affiliation":[{"name":"From the Department of Medicine IV, University of Erlangen, Nu\u0308rnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F.E.","family":"Mann","sequence":"additional","affiliation":[{"name":"From the Department of Medicine IV, University of Erlangen, Nu\u0308rnberg (K.F.H., A.H., M.P., R.V.); the Department of Medicine VI, Schwabing General Hospital, Ludwig-Maximilians-University, Munich (J.F.E.M.); and the German Institute for High Blood Pressure Research, Heidelberg (K.F.H., R.V., J.F.E.M.), Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1976.230.3.849"},{"key":"e_1_3_3_2_2","first-page":"I-63","volume":"3","year":"1981","unstructured":"Dzau VJ, Siwek LG, Rosen S, et al. 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