Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertensionReportar como inadecuado

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, Volume 16, Issue 2, pp 289–295

First Online: 01 December 2012Received: 04 October 2012Accepted: 18 November 2012DOI: 10.1007-s10456-012-9327-4

Cite this article as: Kruzliak, P., Kovacova, G. & Pechanova, O. Angiogenesis 2013 16: 289. doi:10.1007-s10456-012-9327-4


Angiogenesis is critical to tumor growth as well as to metastases. This process is tightly regulated by pro- and anti-angiogenic growth factors and their receptors. Some of these factors are highly specific for the endothelium—e.g., vascular endothelial growth factor VEGF. A variety of drugs that target VEGF or its receptors have been developed for the treatment of different tumor types and a number of new agents is expected to be introduced within the coming years. However, clinical experience has revealed that inhibition of VEGF induces several side effects including hypertension and renal and cardiac toxicity. Angiogenesis-inhibitor-induced hypertension represents -crux medicorum- as it is often pharmacoresistant to antihypertensive therapy. We consider two most important pathomechanisms in the development of hypertension induced by angiogenesis inhibitors. The first represents direct inhibition of NO production leading to reduced vasodilatation and the second consists in increased proliferation of vascular medial cells mediated by NO deficiency and is resulting in fixation of hypertension. Based on the results of experimental and clinical studies as well as on our clinical experience, we assume that NO donors could be successfully used not only for the treatment of developed angiogenesis-inhibitor-induced hypertension but also for preventive effects. We thoroughly documented three clinical cases of cancer patients with resistant hypertension who on receiving NO donor treatment achieved target blood pressure level and a good clinical status.

KeywordsAngiogenesis Vascular endothelial growth factor Anti-angiogenic therapy Nitric oxide donors Cell proliferation  Download fulltext PDF

Autor: Peter Kruzliak - Gabriela Kovacova - Olga Pechanova


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