{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:59:10Z","timestamp":1791118750711,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1999,7]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014Torasemide is a loop diuretic that is effective at low once-daily doses in the treatment of arterial hypertension. Because its antihypertensive mechanism of action may not be based entirely on the elimination of salt and water from the body, a vasodilator effect of this drug can be considered. In the present study, the ability of different concentrations of torasemide to modify angiotensin II (Ang II)\u2013induced vascular responses was examined, with the use of an organ bath system, in endothelium-denuded aortic rings from spontaneously hypertensive rats. Ang II\u2013induced increases of intracellular free calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) were also examined by image analysis in cultured vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A dose-response curve to Ang II was plotted for cumulative concentrations (from 10<jats:sup>\u22129<\/jats:sup>to 10<jats:sup>\u22126<\/jats:sup>mol\/L) in endothelium-denuded aortic rings (pD<jats:sub>2<\/jats:sub>=7.5\u00b10.3). Isometric contraction induced by a submaximal concentration of Ang II (10<jats:sup>\u22127<\/jats:sup>mol\/L) was reduced in a dose-dependent way by torasemide (IC<jats:sub>50<\/jats:sub>=0.5\u00b10.04 \u03bcmol\/L). Incubation of VSMCs with different concentrations of Ang II (from 10<jats:sup>\u221210<\/jats:sup>to 10<jats:sup>\u22126<\/jats:sup>mol\/L) resulted in a dose-dependent rise of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>(pD<jats:sub>2<\/jats:sub>=7.5\u00b10.3). The stimulatory effect of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>induced by a submaximal concentration of Ang II (10<jats:sup>\u22127<\/jats:sup>mol\/L) was blocked by torasemide (IC<jats:sub>50<\/jats:sub>=0.5\u00b10.3 nmol\/L). Our findings suggest that torasemide blocks the vasoconstrictor action of Ang II in vitro. This action can be related to the ability of torasemide to block the increase of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>induced by Ang II in VSMCs. It is proposed that these actions might be involved in the antihypertensive effect of torasemide observed in vivo.<\/jats:p>","DOI":"10.1161\/01.hyp.34.1.138","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"138-143","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Torasemide Inhibits Angiotensin II\u2013Induced Vasoconstriction and Intracellular Calcium Increase in the Aorta of Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"34","author":[{"given":"Ana","family":"Fortun\u0303o","sequence":"first","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Mun\u0303iz","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Ravassa","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Antonio","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma Antonia","family":"Fortun\u0303o","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Zalba","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Di\u0301ez","sequence":"additional","affiliation":[{"name":"From the Vascular Pathophysiology Unit (A.F., P.M., S.R., M.A.F., G.Z., J.D.), and Department of Cardiology (J.A.R.), School of Medicine, University of Navarra, Pamplona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92589-T"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.304.6824.405"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1997.00440420033005"},{"key":"e_1_3_1_4_2","unstructured":"Pecker MS. Pathophysiologic effects and strategies for long-term diuretic treatment of hypertension. In: Laragh JH Brenner BM eds. Hypertension: Pathophysiology Diagnosis and Management. New York NY: Raven Press; 1990:2117\u20132130."},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.27.5.717"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1972.223.5.1049"},{"key":"e_1_3_1_7_2","unstructured":"Weidmann P Beretta-Piccoli C Meier A Keusch G Glueck Z. Untersuchungen zum antihypertensiven mechanismus von diuretika. In: Kruck F Schey A eds. Diuretika II. Munich Germany: Wolf; 1981:58\u201376."},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00582640"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00581840"},{"key":"e_1_3_1_10_2","first-page":"151","volume":"38","year":"1988","unstructured":"Greger R. Inhibition of active NaCl reabsorption in the thick ascending limb of the loop of Henle by torasemide. Arzneimittelf\u00f6rschung. 1988;38:151\u2013152.","journal-title":"Arzneimittelf\u00f6rschung"},{"key":"e_1_3_1_11_2","first-page":"265","volume":"2","year":"1988","unstructured":"Dupont AG, Schoors D, Six RO, Vanhaelst L. Antihypertensive efficacy of low dose torasemide in essential hypertension: a placebo-controlled study. J Hum Hypertens. 1988;2:265\u2013268.","journal-title":"J Hum Hypertens"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","unstructured":"Achhammer I Metz P. Low dose loop diuretics in essential hypertension: experience with torasemide. Drugs. 1991;41(suppl 3):80\u201391.","DOI":"10.2165\/00003495-199100413-00009"},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","unstructured":"Luft FC. Torasemide in the treatment of arterial hypertension. J Cardiovasc Pharmacol. 1993;22(suppl 3):S32\u2013S39.","DOI":"10.1097\/00005344-199322003-00005"},{"key":"e_1_3_1_14_2","first-page":"209","volume":"349","year":"1994","unstructured":"Barthelmebs M, Stephan D, Fontaine C, Grima M, Imbs JL. Vascular effects of loop diuretics: an in vivo and in vitro study in the rat. Naunyn Schmiedebergs Arch Pharmacol. 1994;349:209\u2013216.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.6.1847"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0895-7061(94)00170-G"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.386"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.30.5.1029"},{"key":"e_1_3_1_19_2","first-page":"533","volume":"12","year":"1994","unstructured":"Neusser M, Tepel M, Golinski P, Holthues J, Spieker C, Zhu Z, Zidek W. Different calcium storage pools in vascular smooth muscle cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats. J Hypertens. 1994;12:533\u2013538.","journal-title":"J Hypertens"},{"key":"e_1_3_1_20_2","first-page":"3440","volume":"260","year":"1982","unstructured":"Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1982;260:3440\u20133450.","journal-title":"J Biol Chem"},{"key":"e_1_3_1_21_2","unstructured":"Bartsch W D\u00f6rge L Kling W Schaumann W Gebhardt G Stegmeier K Sponer G. Investigations on the inhibitory activity of torasemide on vasoconstriction induced by KCl noradrenaline endothelin or U 46619 and on platelet aggregation induced by collagen U 44069 or ADP. In: Puschett JB Greenberg AC eds. Diuretics IV: Chemistry Pharmacology and Clinical Applications. New York NY: Elsevier; 1993:349\u2013353."},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.22.6.806"},{"key":"e_1_3_1_23_2","first-page":"313","volume":"57","year":"1997","unstructured":"Peach MJ. Renin-angiotensin system: biochemistry and mechanism of action. Physiol Rev. 1997;57:313\u2013370.","journal-title":"Physiol Rev"},{"key":"e_1_3_1_24_2","first-page":"F759","volume":"250","year":"1986","unstructured":"Smith JB. Angiotensin-receptor signaling in cultured vascular smooth muscle cells. Am J Physiol. 1986;250:F759\u2013F769.","journal-title":"Am J Physiol"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0031-6997(25)00446-6","volume":"45","year":"1993","unstructured":"Timmermans PB, Wong PC, Chin AT, Herblin WF, Benfield P, Carini DI, Lee RJ, Wexler RR, Saya JA, Smith RD. Angiotensin II receptor and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45:205\u2013251.","journal-title":"Pharmacol Rev"},{"key":"e_1_3_1_26_2","unstructured":"Stamler JS Dzau VJ Loscalzo J. The vascular smooth muscle cell. In: Loscalzo J Greger MA Dzau VJ eds. Vascular Medicine. Boston Mass: Little\/Brown; 1996:69\u2013116."},{"key":"e_1_3_1_27_2","first-page":"251","volume":"22","year":"1970","unstructured":"Somlyo AP, Somlyo AV. Vascular smooth muscle. II: pharmacology of normal and hypertensive vessels. Pharmacol Rev. 1970;22:251\u2013353.","journal-title":"Pharmacol Rev"},{"key":"e_1_3_1_28_2","first-page":"606","volume":"59","year":"1970","unstructured":"Bolton TB. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1970;59:606\u2013718.","journal-title":"Physiol Rev"},{"key":"e_1_3_1_29_2","doi-asserted-by":"crossref","unstructured":"Wittner M Di Stefano A Wangemann P Greger R. How do loop diuretics act? Drugs. 1991;41(suppl 3):1\u201313.","DOI":"10.2165\/00003495-199100413-00003"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00587857"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.8.5.379"},{"key":"e_1_3_1_32_2","first-page":"S69","volume":"21","year":"1982","unstructured":"De Mendonca M, Knorr A, Grichois ML, Ben Ishay D, Garay RP, Meyer P. Erythrocytic sodium transport systems in primary and secondary hypertension in the rat. Kidney Int. 1982;21:S69\u2013S75.","journal-title":"Kidney Int"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90307-P"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1983.tb00106.x"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-208-43853"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00370515"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1992.tb14367.x"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)86245-6"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.34.1.138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T21:26:49Z","timestamp":1743370009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.34.1.138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,7]]}},"alternative-id":["10.1161\/01.HYP.34.1.138"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.34.1.138","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,7]]},"assertion":[{"value":"1998-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}