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Inhibitors of Angiogenesis and Blood Pressure

  • Hypertension (M Safar, Section Editor)
  • Published:
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Abstract

Essential hypertension seems to be associated with a reduction (rarefaction) in the number of parallel-connected arterioles and capillaries, with consequent important consequences in terms of tissue perfusion. Antiangiogenic therapies are being increasingly used in the treatment of solid tumors; however, hypertension represents a common side effect of these agents. Mechanisms involved include an impairment of nitric oxide signaling pathway, activation of endothelin system, microvascular rarefaction, the development of salt sensitivity, and an increased oxidative stress; as a consequence an increased blood pressure may be considered a biomarker for cancer response. In the future full understanding of the mechanisms causing antiangiogenic therapy-induced hypertension will provide clinically more useful biomarkers for predicting both toxicity and therapeutic efficacy. On the other hand, early identification and treatment of hypertension are essential to maintain an effective therapeutic dose of these agents, and whether one antihypertensive agent is superior to another in controlling antiangiogenic therapy-induced hypertension remains to be established.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev. 1990;70:921–61.

    PubMed  CAS  Google Scholar 

  2. Schiffrin EL. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am J Hypertens. 2004;17(12 Pt 1):1192–200.

    Article  PubMed  CAS  Google Scholar 

  3. Agabiti Rosei E, Rizzoni D. The effects of hypertension on the structure of human resistance arteries. In: Lip GYH, Hall JE, editors. Comprehensive hypertension. Chapter 47. Philadelphia: Mosby Elsevier; 2007. p. 579–90.

  4. Levy BI, Schiffrin EL, Mourad JJ, Agostini D, Vicaut E, Safar ME, et al. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation. 2008;118:968–76.

    Article  PubMed  Google Scholar 

  5. Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HAJ. Microcirculation in hypertension: a new target for treatment? Circulation. 2001;104:735–40.

    Article  PubMed  CAS  Google Scholar 

  6. Greene AS, Tonellato PJ, Lui J, Lombard JH, Cowley Jr AW. Microvascular rarefaction and tissue vascular resistance in hypertension. Am J Physiol. 1989;256:H126–31.

    PubMed  CAS  Google Scholar 

  7. Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA. Structural skin capillary rarefaction in essential hypertension. Hypertension. 1999;33:998–1001.

    Article  PubMed  CAS  Google Scholar 

  8. Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA. Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. Hypertension. 1999;34(4 Pt 1):655–8.

    Article  PubMed  CAS  Google Scholar 

  9. Debbabi H, Uzan L, Mourad JJ, Safar M, Levy BI, Tibiriçà E. Increased skin capillary density in treated essential hypertensive patients. Am J Hypertens. 2006;19:477–83.

    Article  PubMed  Google Scholar 

  10. Debbabi H, Bonnin P, Levy BI. Effects of blood pressure control with perindopril/indapamide on the microcirculation in hypertensive patients. Am J Hypertens. 2010;23:1136–43.

    Article  PubMed  CAS  Google Scholar 

  11. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6:389–95.

    Article  PubMed  CAS  Google Scholar 

  12. Weigand M, Hantel P, Kreienberg R, Waltenberger J. Autocrine vascular endothelial growth factor signaling in breast cancer. Evidence from cell lines and primary breast cancer cultures in vitro. Angiogenesis. 2005;8:197–204.

    Article  PubMed  CAS  Google Scholar 

  13. • Copur MS, Obermiller A. An algorithm for the management of hypertension in the setting of vascular endothelial growth factor signaling inhibition. Clin Colorectal Cancer. 2011;10:151–6. A paper proposing an algorithm for the management of hypertension during antiangiogenic treatment.

    Article  PubMed  CAS  Google Scholar 

  14. •• de Jesus-Gonzalez N, Robinson E, Moslehi J, Humphreys BD. Management of antiangiogenic therapy-induced hypertension. Hypertension. 2012;60:607–15. A comprehensive review, taking into account available data about the development and management of hypertension during treatment with antiangiogenic drugs.

    Article  PubMed  Google Scholar 

  15. •• Lankhorst S, Kappers MH, van Esch JH, Danser AH, van den Meiracker AH. Mechanism of hypertension and proteinuria during angiogenesis inhibition: evolving role of endothelin-1. J Hypertens. 2013;31:444–54. An updated review dealing with mechanism underlying the development of hypertension and proteinuria during treatment with antiangiogenic drugs, again focusing on the possible role of endothelin-1.

    Article  PubMed  CAS  Google Scholar 

  16. Escalante CP, Zalpour A. Vascular endothelial growth factor inhibitor-induced hypertension: basics for primary care providers. Cardiol Res Pract. 2011;2011:816897.

    PubMed  Google Scholar 

  17. •• Dhaun N, Webb DJ. Receptor tyrosine kinase inhibition, hypertension, and proteinuria: is endothelin the smoking gun? Hypertension. 2010;56:575–7. A very well written editorial commentary on mechanism underlying the development of hypertension and proteinuria during treatment with antiangiogenic drugs, focusing on the possible role of endothelin-1.

    Article  PubMed  CAS  Google Scholar 

  18. Mourad JJ. des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab: a crucial role for microcirculation. Ann Oncol. 2008;19:927–34.

    Article  PubMed  Google Scholar 

  19. Steeghs N, Gelderblom H, Roodt JO, Christensen O, Rajagopalan P, Hovens M, et al. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin Cancer Res. 2008;14:3470–6.

    Article  PubMed  CAS  Google Scholar 

  20. •• Maitland ML, Bakris GL, Black HR, Chen HX, Durand JB, Elliott WJ, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102:596–604. Guidelines of the National Cancer Institute USA management of blood pressure in patients treated with antiangiogenic drugs.

    Article  PubMed  CAS  Google Scholar 

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Conflict of Interest

Damiano Rizzoni declares that he has no conflict of interest.

Anna Paini declares that she has no conflict of interest.

Massimo Salvetti declares that he has no conflict of interest.

Claudia Rossini declares that she has no conflict of interest.

Carolina De Ciuceis declares that she has no conflict of interest.

Claudia Agabiti Rosei declares that she has no conflict of interest.

Maria Lorenza Muiesan declares that she has no conflict of interest.

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Correspondence to Damiano Rizzoni.

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Rizzoni, D., Paini, A., Salvetti, M. et al. Inhibitors of Angiogenesis and Blood Pressure. Curr Cardiovasc Risk Rep 7, 244–247 (2013). https://doi.org/10.1007/s12170-013-0309-x

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  • DOI: https://doi.org/10.1007/s12170-013-0309-x

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