VEGFA and hypertensive disorder: Prevailing theories include: (1) VEGF blockade, which prevents nitric oxide synthetase production of nitric oxide, allowing endothelin driven vasoconstriction; (2) decreased VEGF which may remodel capillaries and lead to endothelial dysfunction; or perhaps (3) TKIs may induce tumor cell apoptosis, leading to release of stored catecholamines and thus hypertension [39].