Angiotensin II in Septic Shock

Corrêa, Thiago Domingos; Takala, Jukka; Jakob, Stephan M.

doi:10.1007/978-3-319-13761-2_10

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…RAS activation as evidenced by increased PRA and Ang II is a well‐known phenomenon observed during the development of sepsis, both in experimental 31,32 . and clinical studies 17,33,34 .…”

Section: Discussionmentioning

confidence: 99%

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner during sepsis

Liu

Mao

et al. 2021

J Cellular Molecular Medi

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Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin‐angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis‐associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration‐dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS‐induced platelet apoptosis and alleviated sepsis‐associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration‐dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner in sepsis‐associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis‐associated thrombocytopenia.

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Section: Discussionmentioning

confidence: 99%

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner during sepsis

Liu

Mao

et al. 2021

J Cellular Molecular Medi

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“…19-21 However, high doses of vasoconstrictors are associated with detrimental side effects, such as atrial fibrillation, cardiac ischemia, and mesenteric ischemia, and have been associated with increased mortality. 22-25 These vasopressors only target the sympathetic and arginine-vasopressin systems and do not have any activity on the RAAS. Vasopressor agents targeting the RAAS have been unavailable to clinicians for the past 20 years, but with the approval of Ang-2 by the Food and Drug Administration (FDA) in 2017, and now the European Medicines Agency in 2019, clinicians can now simultaneously target all 3 systems during septic shock.…”

Section: Discussionmentioning

confidence: 99%

“…Sepsis is characterized by arterial vasodilatation and hypovolemia, and the RAAS is upregulated to restore vascular tone. 25 However, in septic shock, the RAAS fails to adequately compensate for the profound decrease in SVR. Angiotensin II type 1 (AT 1 ) receptors normally cause vasoconstriction through a phospholipase C and inositol triphosphate–mediated pathway and become downregulated and dysfunctional in septic shock.…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensinogen, an α-2 globulin, is produced in the liver and is the only precursor to all downstream angiotensin peptides such as Ang-1 and Ang-2 (Figure 1). 25,33 Hepatocytes are the major producer of angiotensinogen in the body, although synthesis of angiotensinogen has also been described in the proximal tubule and in adipocytes. 9 In liver failure, renin production is upregulated in response to the pathologic decrease in SVR and the perceived decrease in effective circulating blood volume.…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock

Coleman

Nissen

Kim

et al. 2019

Semin Cardiothorac Vasc Anesth

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This case describes the first reported use of human-derived synthetic angiotensin II (Ang-2) in a patient with decompensated cirrhosis and septic shock. The patient presented in vasodilatory shock from Enterobacter cloacae bacteremia with a Sequential Organ Failure Assessment Score of 14 and a Model for End-Stage Liver Disease score of 36. This case is significant because liver failure was an exclusion criterion in the Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) trial, but the liver produces angiotensinogen, which is key precursor to Ang-2 in the renin-angiotensin-aldosterone system. Resuscitation with Ang-2 is a potentially beneficial medication when conventional vasopressors have failed to control mean arterial pressure in this population.

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“…Angiotensin II as a potent vasoconstrictor will likely be appropriate because cotherapy in conditions in which cardiac contractility is reduced. 152,153 Additionally, as discussed, cross-talk exists between angiotensin II and aldosterone beyond the role of the latter in mineralocorticoid effects, the implications and clinical relevance of which remain uncertain. Angiotensin acts on the zona glomerulosa, stimulating the release of aldosterone, which leads to increased sodium reabsorption and a subsequent increase in extracellular and blood fluid volume.…”

Section: Novel Therapeutic Optionsmentioning

confidence: 99%

Mineralocorticoid Dysfunction during Critical Illness

Nethathe¹,

Cohen²,

Lipman³

et al. 2020

Anesthesiology

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The recent demonstration of the significant reduction in mortality in patients with septic shock treated with adjunctive glucocorticoids combined with fludrocortisone and the effectiveness of angiotensin II in treating vasodilatory shock have renewed interest in the role of the mineralocorticoid axis in critical illness. Glucocorticoids have variable interactions at the mineralocorticoid receptor. Similarly, mineralocorticoid receptor–aldosterone interactions differ from mineralocorticoid receptor–glucocorticoid interactions and predicate receptor–ligand interactions that differ with respect to cellular effects. Hyperreninemic hypoaldosteronism or selective hypoaldosteronism, an impaired adrenal response to increasing renin levels, occurs in a subgroup of hemodynamically unstable critically ill patients. The suggestion is that there is a defect at the level of the adrenal zona glomerulosa associated with a high mortality rate that may represent an adaptive response aimed at increasing cortisol levels. Furthermore, cross-talk exists between angiotensin II and aldosterone, which needs to be considered when employing therapeutic strategies.

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Angiotensin II in Septic Shock

Abstract: This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at

Cited by 7 publications

References 42 publications

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner during sepsis

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R‐dependent manner during sepsis

Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock

Mineralocorticoid Dysfunction during Critical Illness

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