Abstract
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.
Highlights
Vessel formation occurs mainly through two sequential mechanisms: vasculogenesis—de novo formation of blood vessels during embryonic development, and angiogenesis—formation of new capillaries from preexisting vessels [1]
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
Because endothelial nitric oxide synthase (eNOS) is upregulated by vascular endothelial growth factor (VEGF), inhibition of VEGF by neutralizing antibodies or a VEGF receptors (VEGFRs) blocker leads to a decrease in nitric oxide production in endothelial cells that may account for the development of hypertension [23]
Summary
Vessel formation occurs mainly through two sequential mechanisms: vasculogenesis—de novo formation of blood vessels during embryonic development, and angiogenesis—formation of new capillaries from preexisting vessels [1]. G. Kovacova 5th, Department of Internal Medicine, University Hospital, Bratislava, Slovak Republic our clinical experience, we assume that NO donors could be successfully used for the treatment of developed angiogenesis-inhibitor-induced hypertension and for preventive effects. Keywords Angiogenesis Á Vascular endothelial growth factor Á Anti-angiogenic therapy Á Nitric oxide donors Á Cell proliferation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
