Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension.
Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension.
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DOI：
10.1007/s10456-012-9327-4
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发表时间：
2013-04
期刊：
影响因子：
9.8
通讯作者：
Pechanova, Olga
中科院分区：
文献类型：
--
作者：
Kruzliak, Peter;Kovacova, Gabriela;Pechanova, Olga
关键词：
血管生成是肿瘤生长和转移的关键。这一过程受到促血管生成和抗血管生成生长因子及其受体的严格调控。其中一些因素对内皮细胞是高度特异性的。，血管内皮生长因子（VEGF）。针对VEGF或其受体的多种药物已被开发出来用于治疗不同类型的肿瘤，预计在未来几年内将推出许多新药。然而，临床经验表明，抑制VEGF可引起高血压、肾和心脏毒性等副作用。血管生成抑制剂诱导的高血压是“关键的药物”，因为它通常对抗高血压治疗具有耐药性。我们认为血管生成抑制剂诱发高血压的两个最重要的病理机制。第一种是直接抑制NO生成导致血管舒张减少，第二种是由NO缺乏介导的血管内侧细胞增殖增加，导致高血压固定。根据实验和临床研究的结果以及我们的临床经验，我们认为NO供体不仅可以成功地用于治疗血管生成抑制剂诱导的高血压，还可以成功地用于预防高血压。我们详细记录了3例肿瘤合并顽固性高血压患者经NO供体治疗后血压达到目标水平，临床状态良好。
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.
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