Vascular endothelial growth factor inhibitor-induced hypertension: from pathophysiology to prevention and treatment based on long-acting nitric oxide donors

Am J Hypertens. 2014 Jan;27(1):3-13. doi: 10.1093/ajh/hpt201. Epub 2013 Oct 29.

Abstract

Hypertension is the most common adverse effect of the inhibitors of vascular endothelial growth factor (VEGF) pathway-based therapy (VEGF pathway inhibitors therapy, VPI therapy) in cancer patients. VPI includes monoclonal antibodies against VEGF, tyrosine kinase inhibitors, VEGF Traps, and so-called aptamers that may become clinically relevant in the future. All of these substances inhibit the VEGF pathway, which in turn causes a decrease in nitric oxide (NO) and an increase in blood pressure, with the consequent development of hypertension and its final events (e.g., myocardial infarction or stroke). To our knowledge, there is no current study on how to provide an optimal therapy for patients on VPI therapy with hypertension. This review summarizes the roles of VEGF and NO in vessel biology, provides an overview of VPI agents, and suggests a potential treatment procedure for patients with VPI-induced hypertension.

Keywords: NO donors; VEGF.; angiogenesis inhibitors; blood pressure; hypertension; nitric oxide (NO).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Hypertension / prevention & control
  • Molecular Targeted Therapy / adverse effects*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / therapeutic use*
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antihypertensive Agents
  • Nitric Oxide Donors
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide