High blood pressure induced by antiangiogenic therapy in the oncologic patient
Keywords:
Hypertension, Angiogenesis Inhibitors, Endothelin-1, Vascular Endothelial Growth Factor A, Neoplasm.Abstract
Introduction: high blood pressure is a multifactorial disease; there is a wide range of stimuli that can trigger it, including drugs.
Objective: to describe the pathophysiological mechanisms involved in the development of hypertension induced by treatment with antiangiogenic drugs in oncological patients.
Methods: a search for information was carried out in the PubMed/MEDLINE, SciELO and Scopus databases. Twenty-four bibliographic references were chosen.
Development: the mechanisms of blood pressure elevation in patients treated with antiangiogenic agents are multifactorial. The mechanisms involved are not seen in isolation, but some are cause and/or effect of others. This interrelationship is shown during inhibition of vascular endothelial growth factor A, which is associated with a decrease in serum levels of nitric oxide metabolites, which triggers sodium retention and increased local and systemic blood pressure, showing changes in renal dynamics. Monitoring is necessary to allow early diagnosis and adequate treatment. This suggests that the use of appropriate antihypertensive drugs may be necessary for maintenance therapy to avoid dose interruption/discontinuation.
Conclusions: there are several pathophysiological mechanisms related to the development of hypertension during treatment with antiangiogenic drugs such as induction of vascular endothelial growth factor A, variations in nitric oxide production, increased expression of pre-hypertensive agents such as endothelin-1, microvascular rare- fraction, activation of the renin-angiotensin system and oxidative stress.
Downloads
Download data is not yet available.
References
1. Oliveros E, Patel H, Kyung S, Fugar S, Goldberg A, Madan N, et al. Hypertension in older adults: Assessment, management, and challenges. Clinical Cardiology [Internet]. 2019 [citado 11/05/21]; 43(2):99-107. Disponible en: https://doi.org/10.1002/clc.23303
2. American Heart Association. High Blood Pressure [Internet]. www.heart.org. 2019. Available from: https://www.heart.org/en/health-topics/high-blood-pressure
3. Jordan J, Kurschat C, Reuter H. Arterial Hypertension. Dtsch Arztebl Int[Internet]. 2018 [citado 11/05/21]; 115(33-34):557-568. Disponible en: https://doi.org/10.3238/arztebl.2018.0557
4. OMS. Hipertensión [Internet]. 2019 [citado 11/05/21]. Disponibe en: https://www.who.int/es/news-room/fact-sheets/detail/hypertension#
5. Hausman DM. What Is Cancer? Perspect Biol Med [Internet]. 2019 [citado 11/05/21]; 62(4):778-784. Disponible en: https://muse.jhu.edu/article/740322
6. Winter MP, Sharma S, Altmann J, Seidl V, Panzenböck A, Alimohammadi A, et al. Interruption of vascular endothelial growth factor receptor 2 signaling induces a proliferative pulmonary vasculopathy and pulmonary hypertension. Basic Res Cardiol [Internet]. 2020 [citado 11/05/21]; 115(6):58. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471204/
7. Li T, Kang G, Wang T, Huang H. Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review). ONCOLOGY LETTERS [Internet]. 2018 [citado 11/05/21]; 16(1):687-702. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019900/#!po=0.304878
8. Touyz RM, Lang NN, Herrmann J, van den Meiracker AH, Danser AHJ. Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition. Hypertension [Internet]. 2017 [citado 11/05/21]; 70(2):220-226. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509510/
9. Touyz RM, Herrmann SMS, Herrmann J. Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. J Am Soc Hypertens [Internet]. 2018 [citado 11/05/21]; 12(6):409-425. Disponible en: https://doi.org/10.1016/j.jash.2018.03.008.
10. Estrada CC, Maldonado A, Mallipattu SK. Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities. J Am Soc Nephrol [Internet]. 2019 [citado 11/05/21]; 30(2):187-200. Disponible en: https://doi.org/10.1681/ASN.2018080853
11. Lankhorst S, Severs D, Markó L, Rakova N, Titze J, Müller DN, et al. Salt Sensitivity of Angiogenesis Inhibition-Induced Blood Pressure Rise: Role of Interstitial Sodium Accumulation? Hypertension [Internet]. 2017 [citado 11/05/21]; 69(5):919-926. Disponible en: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.116.08565?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
12. Caletti S, Paini A, Coschignano MA, Ciuceis Cd, Nardin M, Zulli R, et al. Management of VEGF-Targeted Therapy-Induced Hypertension Current Hypertension Reports [Internet]. 2018 [citado 11/05/21]; 20(8):1-68. Disponible en: https://doi.org/10.1007/s11906-018-0871-1
13. Guverich F, Perazella MA. Renal effecrs anti-angiogenesis therapy: update for the internist. Am J Med [Internet]. 2009 [citado 11/05/21]; 122(4):332-8. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S0002-9343(09)00006-0
14. Sanaullah S, Fatema TZ, Michail SL, Nadezhda AG, Constantinos MM. Mechanisms of angiogenesis in microbe‑regulated inflammatory and neoplastic conditions. Angiogenesis [Internet] 2017 [citado 11/05/21]; 21(1):1-14. Disponible en: https://doi.org/10.1007/s10456-017-9583-4
15. Victorovich-Garbuzenko D, Olegovich-Arefyev N, Leonidovich-Kazachkov E. Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives. World J Gastroenterol [Internet]. 2018 [citado 11/05/21]; 24(33):3738-3748. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127663/
16. Rees ML, Khakoo AY. Molecular mechanisms of hypertension and heart failure due to antiangiogenic cancer therapies. Heart Fail Clin. [Internet] 2011 [citado 11/05/21]; 7(3):299-311. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1551-7136(11)00024-9
17. Foy MC, Vaishnav J, Sperati CJ. Drug-Induced Hypertension. Endocrinol Metab Clin North Am [Internet]. 2019 [citado 11/05/21]; 48(4):859-873. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S0889-8529(19)30067-2
18. Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J, et al. Mechanisms of VEGF (Vascular Endothelial Growth Factor) Inhibitor-Associated Hypertension and Vascular Disease. Hypertension [Internet]. 2018 [citado 11/05/21]; 71(2):e1-e8. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29279311/
19. Li M, Kroetz DL. Bevacizumab-induced hypertension: Clinical presentation and molecular understanding. Pharmacol Ther [Internet]. 2018 [citado 11/05/21]; 182:152-160. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28882537/
20. Gadd M, Pranavan G, Malik L. Association between tyrosine-kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer. Cancer Rep (Hoboken) [Internet]. 2020 [citado 11/05/21]; 3(5):e1275. Disponible en: https://doi.org/10.1002/cnr2.1275
21. Neves KB, Montezano AC, Lang NN, Touyz RM. Vascular toxicity associated with anti-angiogenic drugs. Clin Sci (Lond) [Internet]. 2020[citado 11/05/21]; 134(18):2503-2520. Disponible en: https://doi.org/10.1042/CS20200308
22. Bæk-Møller N, Budolfsen C, Grimm D, Krüger M, Infanger M, Wehland M, et al. Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment. Int J Mol Sci [Internet]. 2019 [citado 11/05/21]; 20(19):e4712. Disponible en: https://doi.org/10.3390/ijms20194712
23. Collins T, Gray K, Bista M, Skinner M, Hardy C, Wang H, et al. Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension. Br J Pharmacol [Internet]. 2018 [citado 11/05/21]; 175(4):618-630. Disponible: https://doi.org/10.1111/bph.14103
24. Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hypertension and VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibition: effects on renal function. Hypertension. [Internet]. 2017[citado 11/05/21]; 70(3):552-558.Disponible en: https://doi.org/10.1161/HYPERTENSIONAHA.117.09275.
2. American Heart Association. High Blood Pressure [Internet]. www.heart.org. 2019. Available from: https://www.heart.org/en/health-topics/high-blood-pressure
3. Jordan J, Kurschat C, Reuter H. Arterial Hypertension. Dtsch Arztebl Int[Internet]. 2018 [citado 11/05/21]; 115(33-34):557-568. Disponible en: https://doi.org/10.3238/arztebl.2018.0557
4. OMS. Hipertensión [Internet]. 2019 [citado 11/05/21]. Disponibe en: https://www.who.int/es/news-room/fact-sheets/detail/hypertension#
5. Hausman DM. What Is Cancer? Perspect Biol Med [Internet]. 2019 [citado 11/05/21]; 62(4):778-784. Disponible en: https://muse.jhu.edu/article/740322
6. Winter MP, Sharma S, Altmann J, Seidl V, Panzenböck A, Alimohammadi A, et al. Interruption of vascular endothelial growth factor receptor 2 signaling induces a proliferative pulmonary vasculopathy and pulmonary hypertension. Basic Res Cardiol [Internet]. 2020 [citado 11/05/21]; 115(6):58. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471204/
7. Li T, Kang G, Wang T, Huang H. Tumor angiogenesis and anti‑angiogenic gene therapy for cancer (Review). ONCOLOGY LETTERS [Internet]. 2018 [citado 11/05/21]; 16(1):687-702. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019900/#!po=0.304878
8. Touyz RM, Lang NN, Herrmann J, van den Meiracker AH, Danser AHJ. Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition. Hypertension [Internet]. 2017 [citado 11/05/21]; 70(2):220-226. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509510/
9. Touyz RM, Herrmann SMS, Herrmann J. Vascular toxicities with VEGF inhibitor therapies-focus on hypertension and arterial thrombotic events. J Am Soc Hypertens [Internet]. 2018 [citado 11/05/21]; 12(6):409-425. Disponible en: https://doi.org/10.1016/j.jash.2018.03.008.
10. Estrada CC, Maldonado A, Mallipattu SK. Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities. J Am Soc Nephrol [Internet]. 2019 [citado 11/05/21]; 30(2):187-200. Disponible en: https://doi.org/10.1681/ASN.2018080853
11. Lankhorst S, Severs D, Markó L, Rakova N, Titze J, Müller DN, et al. Salt Sensitivity of Angiogenesis Inhibition-Induced Blood Pressure Rise: Role of Interstitial Sodium Accumulation? Hypertension [Internet]. 2017 [citado 11/05/21]; 69(5):919-926. Disponible en: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.116.08565?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
12. Caletti S, Paini A, Coschignano MA, Ciuceis Cd, Nardin M, Zulli R, et al. Management of VEGF-Targeted Therapy-Induced Hypertension Current Hypertension Reports [Internet]. 2018 [citado 11/05/21]; 20(8):1-68. Disponible en: https://doi.org/10.1007/s11906-018-0871-1
13. Guverich F, Perazella MA. Renal effecrs anti-angiogenesis therapy: update for the internist. Am J Med [Internet]. 2009 [citado 11/05/21]; 122(4):332-8. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S0002-9343(09)00006-0
14. Sanaullah S, Fatema TZ, Michail SL, Nadezhda AG, Constantinos MM. Mechanisms of angiogenesis in microbe‑regulated inflammatory and neoplastic conditions. Angiogenesis [Internet] 2017 [citado 11/05/21]; 21(1):1-14. Disponible en: https://doi.org/10.1007/s10456-017-9583-4
15. Victorovich-Garbuzenko D, Olegovich-Arefyev N, Leonidovich-Kazachkov E. Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives. World J Gastroenterol [Internet]. 2018 [citado 11/05/21]; 24(33):3738-3748. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127663/
16. Rees ML, Khakoo AY. Molecular mechanisms of hypertension and heart failure due to antiangiogenic cancer therapies. Heart Fail Clin. [Internet] 2011 [citado 11/05/21]; 7(3):299-311. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1551-7136(11)00024-9
17. Foy MC, Vaishnav J, Sperati CJ. Drug-Induced Hypertension. Endocrinol Metab Clin North Am [Internet]. 2019 [citado 11/05/21]; 48(4):859-873. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S0889-8529(19)30067-2
18. Pandey AK, Singhi EK, Arroyo JP, Ikizler TA, Gould ER, Brown J, et al. Mechanisms of VEGF (Vascular Endothelial Growth Factor) Inhibitor-Associated Hypertension and Vascular Disease. Hypertension [Internet]. 2018 [citado 11/05/21]; 71(2):e1-e8. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29279311/
19. Li M, Kroetz DL. Bevacizumab-induced hypertension: Clinical presentation and molecular understanding. Pharmacol Ther [Internet]. 2018 [citado 11/05/21]; 182:152-160. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28882537/
20. Gadd M, Pranavan G, Malik L. Association between tyrosine-kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer. Cancer Rep (Hoboken) [Internet]. 2020 [citado 11/05/21]; 3(5):e1275. Disponible en: https://doi.org/10.1002/cnr2.1275
21. Neves KB, Montezano AC, Lang NN, Touyz RM. Vascular toxicity associated with anti-angiogenic drugs. Clin Sci (Lond) [Internet]. 2020[citado 11/05/21]; 134(18):2503-2520. Disponible en: https://doi.org/10.1042/CS20200308
22. Bæk-Møller N, Budolfsen C, Grimm D, Krüger M, Infanger M, Wehland M, et al. Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment. Int J Mol Sci [Internet]. 2019 [citado 11/05/21]; 20(19):e4712. Disponible en: https://doi.org/10.3390/ijms20194712
23. Collins T, Gray K, Bista M, Skinner M, Hardy C, Wang H, et al. Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension. Br J Pharmacol [Internet]. 2018 [citado 11/05/21]; 175(4):618-630. Disponible: https://doi.org/10.1111/bph.14103
24. Boursiquot BC, Zabor EC, Glezerman IG, Jaimes EA. Hypertension and VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibition: effects on renal function. Hypertension. [Internet]. 2017[citado 11/05/21]; 70(3):552-558.Disponible en: https://doi.org/10.1161/HYPERTENSIONAHA.117.09275.
Downloads
Published
2021-12-28
How to Cite
1.
Landrove-Escalona EA, Moreira-Díaz LR. High blood pressure induced by antiangiogenic therapy in the oncologic patient. Univ. Méd. Pinareña [Internet]. 2021 Dec. 28 [cited 2025 Jun. 2];18(1):e810. Available from: https://revgaleno.sld.cu/index.php/ump/article/view/810
Issue
Section
Review article
