{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:31:56Z","timestamp":1789565516078,"version":"build-2803163510"},"reference-count":90,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.phrs.2021.105916","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T17:55:35Z","timestamp":1632851735000},"page":"105916","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":26,"special_numbering":"C","title":["Dysregulation of the renin-angiotensin system in septic shock: Mechanistic insights and application of angiotensin II in clinical management"],"prefix":"10.1016","volume":"174","author":[{"given":"Fortunato","family":"Senatore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pitchai","family":"Balakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowraganahalli","family":"Jagadeesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2021.105916_bib1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.phrs.2021.105916_bib2","unstructured":"\u3008https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/sepsis\u3009. (Accessed 30 July 2021)."},{"issue":"10219","key":"10.1016\/j.phrs.2021.105916_bib3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13049-019-0596-4","article-title":"Sepsis: mechanisms of bacterial injury to the patient","volume":"27","author":"Minasyan","year":"2019","journal-title":"Scand. J. Trauma Resusc. Emerg. Med."},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1161\/01.HYP.38.2.177","article-title":"Downregulation of angiotensin II type 1 receptors during sepsis","volume":"38","author":"Bucher","year":"2001","journal-title":"Hypertension"},{"key":"10.1016\/j.phrs.2021.105916_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2020.105409","article-title":"Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications","volume":"167","author":"Ning","year":"2021","journal-title":"Pharmacol. Res."},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib7","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13054-015-0802-3","article-title":"Angiotensin II in septic shock","volume":"19","author":"Corr\u00eaa","year":"2015","journal-title":"Crit. Care"},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1213\/ANE.0000000000004343","article-title":"Reversal of vasodilatory shock: current perspectives on conventional, rescue, and emerging vasoactive agents for the treatment of shock","volume":"130","author":"Chow","year":"2020","journal-title":"Anesth. Analg."},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1517\/14728220903460332","article-title":"Modulation of the renin angiotensin-aldosterone system in sepsis: a new therapeutic approach?","volume":"14","author":"Salgado","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.phrs.2021.105916_bib10","article-title":"Angiotensin II: a review of current literature","author":"Alam","year":"2021","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"issue":"8","key":"10.1016\/j.phrs.2021.105916_bib11","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for Sepsis and septic shock (Sepsis-3)","volume":"315","author":"Shankar-Hari","year":"2016","journal-title":"JAMA"},{"key":"10.1016\/j.phrs.2021.105916_bib12","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/01.hjh.0000226182.60321.69","article-title":"Role of the renin\u2013angiotensin-aldosterone system in vascular remodeling and inflammation: a clinical review","volume":"24","author":"Duprez","year":"2006","journal-title":"J. Hypertens."},{"key":"10.1016\/j.phrs.2021.105916_bib13","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1097\/00003246-199810000-00018","article-title":"Influence of angiotensin-converting enzyme inhibitor enalaprilat on endothelial-derived substances in the critically ill","volume":"26","author":"Boldt","year":"1998","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.0001-5172.2004.00283.x","article-title":"The angiotensin II receptor blocker candesartan improves survival and mesenteric perfusion in an acute porcine endotoxin model","volume":"48","author":"Laesser","year":"2004","journal-title":"Acta Anaesthesiol. Scand."},{"key":"10.1016\/j.phrs.2021.105916_bib15","doi-asserted-by":"crossref","first-page":"F245","DOI":"10.1152\/ajprenal.00477.2006","article-title":"Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2","volume":"293","author":"Gupta","year":"2007","journal-title":"Am. J. Physiol. Ren. Physiol."},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.medin.2016.07.010","article-title":"\u00b4A Castellanos-Ortega, Association between exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prior to septic shock and acute kidney injury","volume":"41","author":"Suberviola","year":"2017","journal-title":"Med. Intensiv."},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib17","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1161\/HYPERTENSIONAHA.119.13197","article-title":"Effect of renin-angiotensin-aldosterone system inhibitors on short-term mortality after Sepsis: a population-based cohort study","volume":"75","author":"Hsu","year":"2020","journal-title":"Hypertension"},{"key":"10.1016\/j.phrs.2021.105916_bib18","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/S0140-6736(95)91933-3","article-title":"Severe septic shock unresponsive to noradrenaline","volume":"346","author":"Wray","year":"1995","journal-title":"Lancet"},{"key":"10.1016\/j.phrs.2021.105916_bib19","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1136\/adc.82.5.388","article-title":"Angiotensin for septic shock unresponsive to noradrenaline","volume":"82","author":"Yunge","year":"2000","journal-title":"Arch. Dis. Child."},{"key":"10.1016\/j.phrs.2021.105916_bib20","doi-asserted-by":"crossref","first-page":"e550","DOI":"10.1097\/CCM.0000000000000397","article-title":"Angiotensin II in septic shock: effects on tissue perfusion, organ function, and mitochondrial respiration in a porcine model of fecal peritonitis","volume":"42","author":"Corr\u00eaa","year":"2014","journal-title":"Crit. Care Med."},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40256-018-0297-9","article-title":"FDA approval of angiotensin II for the treatment of hypotension in adults with distributive shock","volume":"19","author":"Senatore","year":"2019","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"10.1016\/j.phrs.2021.105916_bib22","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/s13054-014-0534-9","article-title":"Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study","volume":"18","author":"Chawla","year":"2014","journal-title":"Crit. Care"},{"issue":"8","key":"10.1016\/j.phrs.2021.105916_bib23","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1097\/CCM.0000000000002441","article-title":"Clinical experience with IV angiotensin II administration: a systematic review of safety","volume":"45","author":"Busse","year":"2017","journal-title":"Crit. Care Med."},{"issue":"10","key":"10.1016\/j.phrs.2021.105916_bib24","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.cellsig.2014.06.011","article-title":"A century old renin\u2013angiotensin system still grows with endless possibilities: AT-1 receptor signaling cascades in cardiovascular physiopathology","volume":"26","author":"Balakumar","year":"2014","journal-title":"Cell Signal."},{"issue":"Pt A","key":"10.1016\/j.phrs.2021.105916_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2017.07.003","article-title":"Renin-angiotensin-aldosterone: an inclusive, an invigorative, an interactive and an interminable system","volume":"125","author":"Balakumar","year":"2017","journal-title":"Pharmacol. Res."},{"issue":"12","key":"10.1016\/j.phrs.2021.105916_bib26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s11906-018-0900-0","article-title":"Inflammation as a regulator of the renin angiotensin system and blood pressure","volume":"20","author":"Satou","year":"2018","journal-title":"Curr. Hypertens. Rep."},{"issue":"5","key":"10.1016\/j.phrs.2021.105916_bib27","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A novel angiotensin-converting enzyme\u2013related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. Res."},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib28","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.ccc.2018.11.002","article-title":"Classic and nonclassic renin-angiotensin systems in the critically ill","volume":"35","author":"Bitker","year":"2019","journal-title":"Crit. Care Clin."},{"issue":"3","key":"10.1016\/j.phrs.2021.105916_bib29","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/j.2040-4603.2014.tb00567.x","article-title":"Classical renin-angiotensin system in kidney physiology","volume":"4","author":"Sparks","year":"2014","journal-title":"Compr. Physiol."},{"key":"10.1016\/j.phrs.2021.105916_bib30","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1681\/ASN.2016101066","article-title":"Immunologic effects of the renin-angiotensin system","volume":"28","author":"Crowley","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"issue":"7","key":"10.1016\/j.phrs.2021.105916_bib31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/emmm.201000080","article-title":"Angiotensin II revisited: new roles in inflammation, immunology and aging","volume":"2","author":"Benigni","year":"2010","journal-title":"EMBO Mol. Med."},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib32","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S1357-2725(02)00271-6","article-title":"Inflammation and angiotensin II","volume":"35","author":"Suzuki","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.phrs.2021.105916_bib33","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2174\/138161212799436593","article-title":"Role of renin-angiotensin system in inflammation, immunity and aging","volume":"18","author":"Capettinia","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.phrs.2021.105916_bib34","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cyto.2009.10.006","article-title":"Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock","volume":"49","author":"Schmidt","year":"2010","journal-title":"Cytokine"},{"key":"10.1016\/j.phrs.2021.105916_bib35","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tips.2008.05.003","article-title":"Role of the renin-angiotensin system in vascular inflammation","volume":"29","author":"Marchesi","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib36","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1161\/HYPERTENSIONAHA.114.03863","article-title":"Tumor necrosis factor-alpha produced in the kidney contributes to angiotensin II-dependent hypertension","volume":"64","author":"Zhang","year":"2014","journal-title":"Hypertension"},{"issue":"9","key":"10.1016\/j.phrs.2021.105916_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0138372","article-title":"Tumor necrosis factor - alpha is essential for angiotensin II-induced ventricular remodeling: role for oxidative stress","volume":"10","author":"Sriramula","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib38","doi-asserted-by":"crossref","first-page":"R24","DOI":"10.1186\/cc8887","article-title":"Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis","volume":"14","author":"Doerschug","year":"2010","journal-title":"Crit. Care"},{"issue":"8\u20139","key":"10.1016\/j.phrs.2021.105916_bib39","first-page":"1493","article-title":"Renin-angiotensin system in sepsis","volume":"9","author":"Hilgenfeldt","year":"1987","journal-title":"Clin. Exp. Hypertens. A"},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s10753-010-9269-1","article-title":"Inflammation alters angiotensin converting enzymes (ACE and ACE-2) balance in rat heart","volume":"34","author":"Hanafy","year":"2011","journal-title":"Inflammation"},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib41","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1074\/jbc.M308697200","article-title":"Tumor necrosis factor-alpha activates NFkappaB to inhibit renin transcription by targeting cAMP-responsive element","volume":"279","author":"Todorov","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.phrs.2021.105916_bib42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cardiores.2004.02.005","article-title":"Cross-regulation between the renin angiotensin system and inflammatory mediators in cardiac hypertrophy and failure","volume":"63","author":"Sekiguchi","year":"2004","journal-title":"Cardiovasc. Res."},{"issue":"1","key":"10.1016\/j.phrs.2021.105916_bib43","first-page":"219","article-title":"Effects of cytokines on the expression of angiotensin II type 1 receptors in vascular smooth muscle cells","volume":"9","author":"Wang","year":"2016","journal-title":"Int. J. Clin. Exp. Med."},{"key":"10.1016\/j.phrs.2021.105916_bib44","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1097\/00003246-200109000-00016","article-title":"Nitric oxide-dependent down-regulation of angiotensin II type 2 receptors during experimental sepsis","volume":"29","author":"Bucher","year":"2001","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib45","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.3892\/etm.2014.1566","article-title":"Severe sepsis: low expression of the renin-angiotensin system is associated with poor prognosis","volume":"7","author":"Zhang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.phrs.2021.105916_bib46","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/cc8185","article-title":"Angiotensin II in experimental hyperdynamic sepsis","volume":"13","author":"Wan","year":"2009","journal-title":"Crit. Care"},{"key":"10.1016\/j.phrs.2021.105916_bib47","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1056\/NEJM199305203282008","article-title":"Pathogenetic mechanisms of septic shock","volume":"328","author":"Parrillo","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phrs.2021.105916_bib48","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.amjhyper.2004.01.003","article-title":"Nitric oxide synthase inhibition accelerates the pressor response to low-dose Angiotensin II, exacerbates target organ damage, and induces renin escape","volume":"17","author":"Hu","year":"2004","journal-title":"Am. J. Hypertens."},{"key":"10.1016\/j.phrs.2021.105916_bib49","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0922-4106(95)90197-3","article-title":"Nitric oxide regulates angiotensin II receptors in vascular smooth muscle cells","volume":"288","author":"Cahill","year":"1995","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.phrs.2021.105916_bib50","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1161\/01.HYP.31.1.342","article-title":"Downregulation of angiotensin II type 1 receptor gene transcription by nitric oxide","volume":"31","author":"Ichiki","year":"1998","journal-title":"Hypertension"},{"key":"10.1016\/j.phrs.2021.105916_bib51","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1139\/y99-037","article-title":"Functional involvement of angiotensin AT2 receptor in adrenal catecholamine secretion in vivo","volume":"77","author":"Martineau","year":"1999","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"10.1016\/j.phrs.2021.105916_bib52","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1097\/shk.0b013e318050c836","article-title":"Role of adenosine triphosphate-sensitive potassium channel inhibition in shock states: physiology and clinical implications","volume":"28","author":"Lange","year":"2007","journal-title":"Shock"},{"issue":"4 Pt 1","key":"10.1016\/j.phrs.2021.105916_bib53","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1152\/ajpcell.1995.268.4.C799","article-title":"Physiological roles and properties of potassium channels in arterial smooth muscle","volume":"268","author":"Nelson","year":"1995","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.phrs.2021.105916_bib54","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1056\/NEJMra032401","article-title":"Acute renal failure and sepsis","volume":"351","author":"Schrier","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.phrs.2021.105916_bib55","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0022-4804(85)90046-0","article-title":"Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect","volume":"38","author":"Fink","year":"1985","journal-title":"J. Surg. Res."},{"key":"10.1016\/j.phrs.2021.105916_bib56","first-page":"H1086","article-title":"Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia","volume":"249","author":"Schaller","year":"1985","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.phrs.2021.105916_bib57","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1038\/sj.bjp.0701751","article-title":"Differential effects of endotoxaemia on pressor and vasoconstrictor actions of angiotensin II and arginine vasopressin in conscious rats","volume":"123","author":"Tarpey","year":"1998","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phrs.2021.105916_bib58","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/00003246-199705000-00025","article-title":"Impaired microvascular vasoconstrictive responses to vasopressin in septic rats","volume":"25","author":"Hollenberg","year":"1997","journal-title":"Crit. Care Med."},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib59","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41569-020-00492-2","article-title":"Pathophysiology of sepsis- induced cardiomyopathy","volume":"18","author":"Hollenberg","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.phrs.2021.105916_bib60","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1056\/NEJMra1208943","article-title":"Circulatory shock","volume":"369","author":"Vincent","year":"2013","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"10.1016\/j.phrs.2021.105916_bib61","doi-asserted-by":"crossref","first-page":"943","DOI":"10.21037\/jtd.2017.03.125","article-title":"SIRS, qSOFA, and new sepsis definition","volume":"9","author":"Marik","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"10.1016\/j.phrs.2021.105916_bib62","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5152\/TJAR.2017.93753","article-title":"Changing definitions of sepsis","volume":"45","author":"G\u00fcl","year":"2017","journal-title":"Turk. J. Anaesthesiol. Reanim."},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib63","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.chest.2017.12.021","article-title":"Management of refractory vasodilatory shock","volume":"154","author":"Jentzer","year":"2018","journal-title":"Chest"},{"issue":"24","key":"10.1016\/j.phrs.2021.105916_bib64","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1001\/jama.1993.03510240069035","article-title":"A new simplified acute physiology score based on a European\/North American multicenter study","volume":"270","author":"Le Gall","year":"1993","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.phrs.2021.105916_bib65","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA (Sepsis-related Organ Failure Assessment)score to describe organ dysfunction\/failure","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib66","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1053\/gast.2003.50016","article-title":"Model for end-stage liver disease (MELD) and allocation of donor livers","volume":"124","author":"Wiesner","year":"2003","journal-title":"Gastroenterology"},{"key":"10.1016\/j.phrs.2021.105916_bib67","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/CCM.0000000000002255","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016","volume":"45","author":"Rhodes","year":"2017","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib68","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1097\/CCM.0000000000003119","article-title":"The surviving sepsis campaign bundle: 2018 update","volume":"46","author":"Levy","year":"2018","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib69","article-title":"Therapeutic strategies for high-dose vasopressor-dependent shock","volume":"2013","author":"Bassi","year":"2013","journal-title":"Crit. Care Res. Pract."},{"key":"10.1016\/j.phrs.2021.105916_bib70","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.jpainsymman.2016.12.333","article-title":"Intensity of vasopressor therapy for septic shock and the risk of in-hospital death","volume":"53","author":"Brand","year":"2017","journal-title":"J. Pain Symptom Manag."},{"key":"10.1016\/j.phrs.2021.105916_bib71","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1097\/ALN.0b013e3182a10e26","article-title":"Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension","volume":"119","author":"Walsh","year":"2013","journal-title":"Anesthesiology"},{"key":"10.1016\/j.phrs.2021.105916_bib72","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1001\/jama.1961.03040490020005","article-title":"Clinical experience with angiotensin II in the treatment of shock","volume":"178","author":"del Greco","year":"1961","journal-title":"JAMA"},{"key":"10.1016\/j.phrs.2021.105916_bib73","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1097\/00003246-199108000-00020","article-title":"Administration of angiotensin II in refractory septic shock","volume":"19","author":"Thomas","year":"1991","journal-title":"Crit. Care Med."},{"key":"10.1016\/j.phrs.2021.105916_bib74","unstructured":"\u3008https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/209360Orig1s000TOC.cfm\u3009. (Accessed 2 August 2021)."},{"key":"10.1016\/j.phrs.2021.105916_bib75","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0024-3205(85)90507-7","article-title":"Relative biological activities of Asn1-,Val5-angiotensin II, Ile5-angiotensin II and Sar1-angiotensin II in man","volume":"37","author":"Kono","year":"1985","journal-title":"Life Sci."},{"key":"10.1016\/j.phrs.2021.105916_bib76","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1042\/cs0420091","article-title":"The role of angiotensin II in the control of aldosterone in man","volume":"42","author":"Boyd","year":"1972","journal-title":"Clin. Sci."},{"key":"10.1016\/j.phrs.2021.105916_bib77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1161\/01.RES.34.1.69","article-title":"Sensitization of the adrenal cortex to angiotensin II in sodium-deplete man","volume":"34","author":"Oelkers","year":"1974","journal-title":"Circ. Res."},{"key":"10.1016\/j.phrs.2021.105916_bib78","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1186\/s13054-017-1896-6","article-title":"The effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literature","volume":"21","author":"Busse","year":"2017","journal-title":"Crit. Care"},{"key":"10.1016\/j.phrs.2021.105916_bib79","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1056\/NEJMoa1704154","article-title":"Angiotensin II for the treatment of vasodilatory shock","volume":"377","author":"Khanna","year":"2017","journal-title":"N. Engl. J. Med."},{"issue":"11","key":"10.1016\/j.phrs.2021.105916_bib80","first-page":"685","article-title":"Angiotensin II brings more questions than answers","volume":"43","author":"Farina","year":"2018","journal-title":"P T"},{"key":"10.1016\/j.phrs.2021.105916_bib81","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/00001721-199901000-00003","article-title":"Acute effects of angiotensin II on fibrinolysis in healthy volunteers","volume":"10","author":"Larsson","year":"1999","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"10.1016\/j.phrs.2021.105916_bib82","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1161\/01.CIR.87.6.1969","article-title":"Stimulation of plasminogen activator inhibitor in vivo by infusion of Angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function","volume":"87","author":"Ridker","year":"1993","journal-title":"Circulation"},{"issue":"7047","key":"10.1016\/j.phrs.2021.105916_bib83","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.phrs.2021.105916_bib84","first-page":"5492.5497","article-title":"Angiotensin-(1-7) prevents lipopolysaccharide-induced hepatocellular inflammatory response by inhibiting the p38MAPK\/AP-1 signaling pathway","volume":"17","author":"Xiao","year":"2018","journal-title":"Mol. Med. Rep."},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib85","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S1474-4422(14)70017-1","article-title":"Long-term cerebral consequences of sepsis","volume":"13","author":"Widmann","year":"2014","journal-title":"Lancet Neurol."},{"issue":"6","key":"10.1016\/j.phrs.2021.105916_bib86","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1042\/CS20140840","article-title":"Endotoxin-induced skeletal muscle wasting is prevented by angiotensin-(1-7) through a p38 MAPK-dependent mechanism","volume":"129","author":"Morales","year":"2015","journal-title":"Clin. Sci."},{"issue":"2","key":"10.1016\/j.phrs.2021.105916_bib87","first-page":"123","article-title":"Evidence for a physiological role of renal sympathetic nerves in adrenergic stimulation of renin release in the rat","volume":"38","author":"Aoi","year":"1976","journal-title":"Circ. Res."},{"issue":"4822","key":"10.1016\/j.phrs.2021.105916_bib88","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1126\/science.3306925","article-title":"Direct demonstration of macula densa-mediated renin secretion","volume":"237","author":"Skott","year":"1987","journal-title":"Science"},{"key":"10.1016\/j.phrs.2021.105916_bib89","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1365-2796.2008.01981.x","article-title":"Renin-angiotensin system revisited","volume":"264","author":"Fyhrquist","year":"2008","journal-title":"J. Intern. Med."},{"key":"10.1016\/j.phrs.2021.105916_bib90","first-page":"412","article-title":"Intrarenal production of angiotensin II","volume":"17","author":"Navar","year":"1997","journal-title":"Semin. Nephrol."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661821005004?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661821005004?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T19:58:28Z","timestamp":1750881508000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661821005004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":90,"alternative-id":["S1043661821005004"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2021.105916","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Dysregulation of the renin-angiotensin system in septic shock: Mechanistic insights and application of angiotensin II in clinical management","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2021.105916","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"105916"}}