{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:59:38Z","timestamp":1789448378779,"version":"build-2803163510"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1997,9,16]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    In humans, hemodynamic changes observed within minutes after systemic administration of furosemide are often referred to as direct vasoactivity. However, these immediate changes do not per se imply a direct vascular effect. We examined the genuine direct vascular effects of furosemide on the human forearm vascular bed and dorsal hand vein.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    Forearm blood flow in response to infusion of increasing dosages of furosemide into the brachial artery was recorded by venous occlusion plethysmography. Local plasma concentrations of furosemide reached a maximum of 234\u00b140 \u03bcg\/mL during the highest infused dose but did not significantly affect the ratio of flow in the infused\/noninfused arms. Venous distensibility of a dorsal hand vein was measured with a linear variable differential transformer. During precontraction with norepinephrine, five increasing dosages of furosemide (1 to 100 \u03bcg\/min) were administered locally. Additional experiments using local administration of indomethacin or\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>G<\/jats:sup>\n                    -monomethyl-\n                    <jats:sc>l<\/jats:sc>\n                    -arginine (L-NMMA) were carried out to determine whether effects were dependent on local prostaglandin or nitric oxide synthesis, respectively. Also, the effects of systemic administration of furosemide were examined. Local administration of furosemide led to a dose-dependent venorelaxation of 18\u00b16% at the first to 72\u00b116% at the last dose. Indomethacin almost completely abolished furosemide-induced venorelaxation, whereas L-NMMA had no effect. Systemic administration of furosemide resulted in a time-dependent increase of hand vein distensibility, reaching 45\u00b111% after 8 minutes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    Furosemide does not exert any direct arterial vasoactivity in the human forearm, even at supratherapeutic concentrations. In contrast, at concentrations estimated to be in the therapeutic range, we observed a dose-dependent direct venodilator effect on the dorsal hand vein that appears to be mediated by local vascular prostaglandin synthesis.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.96.6.1847","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:41:02Z","timestamp":1339447262000},"page":"1847-1852","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":105,"title":["Direct Vascular Effects of Furosemide in Humans"],"prefix":"10.1161","volume":"96","author":[{"given":"Peter","family":"Pickkers","sequence":"first","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom P. J.","family":"Dormans","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G. M.","family":"Russel","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alun D.","family":"Hughes","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Thien","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas","family":"Schaper","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Smits","sequence":"additional","affiliation":[{"name":"From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary\u2019s Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197305242882102"},{"key":"e_1_3_2_2_2","first-page":"551","volume":"31","year":"1969","unstructured":"Bhatia ML, Singh I, Manchanda SC, Khanna PK, Roy SB. Effect of frusemide on pulmonary blood volume. Br Med J. 1969;31:551-552.","journal-title":"Br Med J"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.53.5.6414733"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0650359"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365517609068014"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(79)90217-6"},{"key":"e_1_3_2_7_2","first-page":"406","volume":"68","year":"1991","unstructured":"Tian R, Aalkj\u00e6r C, Andreasen F. Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery. Pharmacol Toxicol. 1991;68:406-410.","journal-title":"Pharmacol Toxicol"},{"key":"e_1_3_2_8_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;349:209-216.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0022-3565(25)22511-3","volume":"270","year":"1994","unstructured":"Greenberg S, McGowan C, Xie J, Summer WR. Selective pulmonary and venous smooth muscle relaxation by furosemide: a comparison with morphine. J Pharmacol Exp Ther. 1994;270:1077-1085.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198707000-00006"},{"key":"e_1_3_2_11_2","first-page":"1","volume":"121","year":"1953","unstructured":"Whitney RJ. The measurement of volume changes in human limbs. J Physiol Camb. 1953;121:1-27.","journal-title":"J Physiol Camb"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0800413"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)82572-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1984.tb16496.x"},{"key":"e_1_3_2_15_2","first-page":"321","volume":"7","year":"1985","unstructured":"Aellig WH. Methods for studying drug effects on superficial human veins. Methods Find Exp Clin Pharmacol. 1985;7:321-324.","journal-title":"Methods Find Exp Clin Pharmacol"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1985.214"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0430455"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/S0022-3565(25)24048-4","volume":"271","year":"1994","unstructured":"Wiemer G, Fink E, Linz W, Hropot M, Scholkens BE, Wohlfart P. Furosemide enhances the release of endothelial kinins, nitric oxide and prostacyclin. J Pharmacol Exp Ther. 1994;271:1611-1615.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_19_2","first-page":"S182","volume":"17","year":"1991","unstructured":"Collier J, Vallance P. L-NMMA increases arteriolar but not venous tone in humans: the mechanism appears to be appendent of sympathetic tone. J Cardiovasc Pharmacol. 1991;17:S182-S185.","journal-title":"J Cardiovasc Pharmacol"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/23.12.1053"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1954.sp005177"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1984.tb05024.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/13.1.16"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.44"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1978.tb01595.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90200-3"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.3.683"},{"key":"e_1_3_2_28_2","first-page":"138","volume":"28","year":"1991","unstructured":"O\u2019Donnell ME, Owen NE. Sodium cotransport in vascular smooth muscle cells. Blood Vessels. 1991;28:138-146.","journal-title":"Blood Vessels"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47066-X"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1982.tb08771.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0022-3565(25)20986-7","volume":"246","year":"1988","unstructured":"Lundergan CF, Fitzpatrick TM, Rose JC, Ramwell PW, Kot PA. Effect of cyclooxygenase inhibition on the pulmonary vasodilator response to furosemide. J Pharmacol Exp Ther. 1988;246:102-106.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb11998.x"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.96.6.1847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T16:41:16Z","timestamp":1743352876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.96.6.1847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,9,16]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1997,9,16]]}},"alternative-id":["10.1161\/01.CIR.96.6.1847"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.96.6.1847","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,9,16]]},"assertion":[{"value":"1997-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1997-09-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}