Why Angiotensin II is a Poor Choice for Circulatory Support of Ventilated COVID-19 Patients Compared to Vasopressin
Main Article Content
Abstract
Early in the COVID-19 pandemic when it was first reported that SARS-CoV-2 used membrane-bound angiotensin-converting enzyme-2 (ACE2) as its receptor for entry into cells, warnings were raised against the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) because of their potential to increase ACE2 expression. These reports ignored the adverse effects that the renin-angiotensin system (RAS) exerts on the cardiovascular system and kidneys via its primary hormone angiotensin (Ang) II acting upon AT1 receptors that could exacerbate the cytokine storm induced by SARS-CoV-2 1. At one point it was even recommended that COVID-19 patients suffering from cardiovascular collapse be administered Ang II to restore blood pressure rather than norepinephrine or vasopressin 2. An alternative strategy for treating COVID-19 was the administration of soluble ACE2 (sACE2) to act as a decoy receptor for the virus, misdirecting it away from vulnerable cells expressing membrane bound ACE2 3-5. However, a paper published in early 2021 6 described a scenario in which sACE2 and vasopressin played essential roles in SARS-CoV-2 infection of cells vulnerable to the virus. This commentary challenges both the 2 and 6 reports based upon their misconceptions and technical errors that pose a threat to the administration of life-saving therapies for severely affected COVID-19 patients.
Article Details
How to Cite
SPETH, Robert C.; BADER, Michael.
Why Angiotensin II is a Poor Choice for Circulatory Support of Ventilated COVID-19 Patients Compared to Vasopressin.
Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3079>. Date accessed: 27 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i9.3079.
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The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Speth RC. Angiotensin II administration to COVID-19 patients is not advisable. Crit Care. 2020;24:296.
2. Busse LW, Chow JH, McCurdy MT and Khanna AK. COVID-19 and the RAAS—a potential role for angiotensin II? Critical Care. 2020;24:136.
3. Batlle D, Wysocki J and Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clinical science (London, England : 1979). 2020;134:543-545.
4. Krishnamurthy S, Lockey RF and Kolliputi N. Soluble ACE2 as a potential therapy for COVID-19. Am J Physiol Cell Physiol. 2021;320:C279-c281.
5. Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS and Penninger JM. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med. 2020;8:1154-1158.
6. Yeung ML, Teng JLL, Jia L, Zhang C, Huang C, Cai J-P, Zhou R, Chan K-H, Zhao H, Zhu L, Siu K-L, Fung S-Y, Yung S, Chan TM, To KK-W, Chan JF-W, Cai Z, Lau SKP, Chen Z, Jin D-Y, Woo PCY and Yuen K-Y. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell. 2021;184:2212-2228.e12.
7. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H and Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450-454.
8. Verano-Braga T, Martins ALV, Motta-Santos D, Campagnole-Santos MJ and Santos RAS. ACE2 in the renin-angiotensin system. Clinical science (London, England : 1979). 2020;134:3063-3078.
9. Speth RC. Renin-Angiotensin-Aldosterone System. In: K. T, ed. Comprehensive Pharmacology: Elsevier; 2022(4): 528-569.
10. Forrester SJ, Booz GW, Sigmund CD, Coffman TM, Kawai T, Rizzo V, Scalia R and Eguchi S. Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology. Physiological reviews. 2018;98:1627-1738.
11. Dalan R, Bornstein SR, El-Armouche A, Rodionov RN, Markov A, Wielockx B, Beuschlein F and Boehm BO. The ACE-2 in COVID-19: Foe or Friend? Horm Metab Res. 2020;52:257-263.
12. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C and Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112-116.
13. Wan Y, Shang J, Graham R, Baric RS and Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. 2020;94:e00127-20.
14. Zhang H, Penninger JM, Li Y, Zhong N and Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine. 2020;46:586-590.
15. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W and Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.
16. Verdecchia P, Cavallini C, Spanevello A and Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. European journal of internal medicine. 2020;76:14-20.
17. Banu N, Panikar SS, Leal LR and Leal AR. Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications. Life Sci. 2020;256:117905.
18. Leisman DE, Mastroianni F, Fisler G, Shah S, Hasan Z, Narasimhan M, Taylor MD and Deutschman CS. Physiologic Response to Angiotensin II Treatment for Coronavirus Disease 2019-Induced Vasodilatory Shock: A Retrospective Matched Cohort Study. Crit Care Explor. 2020;2:e0230.
19. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF and Deane AM. Angiotensin II for the Treatment of Vasodilatory Shock. The New England journal of medicine. 2017;377:419-430.
20. Chammas J, Delaney D, Chabaytah N, Abdulkarim S and Schwertani A. COVID-19 and the cardiovascular system: insights into effects and treatments. Canadian journal of physiology and pharmacology. 2021;99:1119-1127.
21. Manzur-Pineda K, O'Neil CF, Bornak A, Lalama MJ, Shao T, Kang N, Kennel-Pierre S, Tabbara M, Velazquez OC and Rey J. COVID-19 Related Thrombotic Complications Experience Before and During Delta Wave. J Vasc Surg. 2022.
22. Ruster C and Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. JAmSocNephrol. 2006;17:2985-2991.
23. Karnik SS, Unal H, Kemp JR, Tirupula KC, Eguchi S, Vanderheyden PM and Thomas WG. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli. Pharmacological reviews. 2015;67:754-819.
24. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Laderchi A, Bachetoni A, D'Alessandro M, Van Aken H, Pietropaoli P and Westphal M. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care. 2008;12:R143.
25. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D'Egidio A, D'Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A and Singer M. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683-91.
26. Hofmann H, Geier M, Marzi A, Krumbiegel M, Peipp M, Fey GH, Gramberg T and Pöhlmann S. Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochem Biophys Res Commun. 2004;319:1216-21.
27. Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M and Campagnole-Santos MJ. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiological reviews. 2018;98:505-553.
28. Leisman DE, Mehta A, Li Y, Kays KR, Li JZ, Filbin MR and Goldberg MB. Vasopressin infusion in COVID-19 critical illness is not associated with impaired viral clearance: a pilot study. Br J Anaesth. 2021;127:e146-e148.
29. Lipworth BJ and Dagg KD. Vasoconstrictor effects of angiotensin II on the pulmonary vascular bed. Chest. 1994;105:1360-4.
30. Batlle D, Monteil V, Garreta E, Hassler L, Wysocki J, Chandar V, Schwartz RE, Mirazimi A, Montserrat N, Bader M and Penninger JM. Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity. Cell. 2022;185:1837-1839.
2. Busse LW, Chow JH, McCurdy MT and Khanna AK. COVID-19 and the RAAS—a potential role for angiotensin II? Critical Care. 2020;24:136.
3. Batlle D, Wysocki J and Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clinical science (London, England : 1979). 2020;134:543-545.
4. Krishnamurthy S, Lockey RF and Kolliputi N. Soluble ACE2 as a potential therapy for COVID-19. Am J Physiol Cell Physiol. 2021;320:C279-c281.
5. Zoufaly A, Poglitsch M, Aberle JH, Hoepler W, Seitz T, Traugott M, Grieb A, Pawelka E, Laferl H, Wenisch C, Neuhold S, Haider D, Stiasny K, Bergthaler A, Puchhammer-Stoeckl E, Mirazimi A, Montserrat N, Zhang H, Slutsky AS and Penninger JM. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respir Med. 2020;8:1154-1158.
6. Yeung ML, Teng JLL, Jia L, Zhang C, Huang C, Cai J-P, Zhou R, Chan K-H, Zhao H, Zhu L, Siu K-L, Fung S-Y, Yung S, Chan TM, To KK-W, Chan JF-W, Cai Z, Lau SKP, Chen Z, Jin D-Y, Woo PCY and Yuen K-Y. Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell. 2021;184:2212-2228.e12.
7. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H and Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450-454.
8. Verano-Braga T, Martins ALV, Motta-Santos D, Campagnole-Santos MJ and Santos RAS. ACE2 in the renin-angiotensin system. Clinical science (London, England : 1979). 2020;134:3063-3078.
9. Speth RC. Renin-Angiotensin-Aldosterone System. In: K. T, ed. Comprehensive Pharmacology: Elsevier; 2022(4): 528-569.
10. Forrester SJ, Booz GW, Sigmund CD, Coffman TM, Kawai T, Rizzo V, Scalia R and Eguchi S. Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology. Physiological reviews. 2018;98:1627-1738.
11. Dalan R, Bornstein SR, El-Armouche A, Rodionov RN, Markov A, Wielockx B, Beuschlein F and Boehm BO. The ACE-2 in COVID-19: Foe or Friend? Horm Metab Res. 2020;52:257-263.
12. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C and Penninger JM. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112-116.
13. Wan Y, Shang J, Graham R, Baric RS and Li F. Receptor recognition by novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS. J Virol. 2020;94:e00127-20.
14. Zhang H, Penninger JM, Li Y, Zhong N and Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine. 2020;46:586-590.
15. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W and Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565-574.
16. Verdecchia P, Cavallini C, Spanevello A and Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. European journal of internal medicine. 2020;76:14-20.
17. Banu N, Panikar SS, Leal LR and Leal AR. Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications. Life Sci. 2020;256:117905.
18. Leisman DE, Mastroianni F, Fisler G, Shah S, Hasan Z, Narasimhan M, Taylor MD and Deutschman CS. Physiologic Response to Angiotensin II Treatment for Coronavirus Disease 2019-Induced Vasodilatory Shock: A Retrospective Matched Cohort Study. Crit Care Explor. 2020;2:e0230.
19. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hästbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF and Deane AM. Angiotensin II for the Treatment of Vasodilatory Shock. The New England journal of medicine. 2017;377:419-430.
20. Chammas J, Delaney D, Chabaytah N, Abdulkarim S and Schwertani A. COVID-19 and the cardiovascular system: insights into effects and treatments. Canadian journal of physiology and pharmacology. 2021;99:1119-1127.
21. Manzur-Pineda K, O'Neil CF, Bornak A, Lalama MJ, Shao T, Kang N, Kennel-Pierre S, Tabbara M, Velazquez OC and Rey J. COVID-19 Related Thrombotic Complications Experience Before and During Delta Wave. J Vasc Surg. 2022.
22. Ruster C and Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. JAmSocNephrol. 2006;17:2985-2991.
23. Karnik SS, Unal H, Kemp JR, Tirupula KC, Eguchi S, Vanderheyden PM and Thomas WG. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli. Pharmacological reviews. 2015;67:754-819.
24. Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Laderchi A, Bachetoni A, D'Alessandro M, Van Aken H, Pietropaoli P and Westphal M. Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. Crit Care. 2008;12:R143.
25. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D'Egidio A, D'Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A and Singer M. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683-91.
26. Hofmann H, Geier M, Marzi A, Krumbiegel M, Peipp M, Fey GH, Gramberg T and Pöhlmann S. Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochem Biophys Res Commun. 2004;319:1216-21.
27. Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M and Campagnole-Santos MJ. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiological reviews. 2018;98:505-553.
28. Leisman DE, Mehta A, Li Y, Kays KR, Li JZ, Filbin MR and Goldberg MB. Vasopressin infusion in COVID-19 critical illness is not associated with impaired viral clearance: a pilot study. Br J Anaesth. 2021;127:e146-e148.
29. Lipworth BJ and Dagg KD. Vasoconstrictor effects of angiotensin II on the pulmonary vascular bed. Chest. 1994;105:1360-4.
30. Batlle D, Monteil V, Garreta E, Hassler L, Wysocki J, Chandar V, Schwartz RE, Mirazimi A, Montserrat N, Bader M and Penninger JM. Evidence in favor of the essentiality of human cell membrane-bound ACE2 and against soluble ACE2 for SARS-CoV-2 infectivity. Cell. 2022;185:1837-1839.