Treatment with angiogenesis inhibitors (VEGF antibodies (Abs), VEGFR Ab, VEGF trap, or TKIs), as well as elevated levels of sFlt-1 (a soluble VEGFR) in preeclampsia all lead to disturbed VEGF signaling, thereby increasing ET-1. This causes hypertension and renal injury via endothelin type A (ET_A) receptor stimulation. Such stimulation is accompanied by reactive oxygen species (ROS) formation and COX type 1 and type 2 (COX-1/COX-2)-mediated PGI₂ production. Normally, binding of PGI₂ to its prostacyclin (IP) receptor results in beneficial vascular and renal effects, and thus initially this may be protective. Yet, in case of excessive PGI₂ production, PGI₂ can additionally stimulate other prostanoid receptors such as the thromboxane (TP) receptor, the main signaling receptor for TXA₂, acting as an endothelium-derived contracting factor (EDCF). This could contribute to angiogenesis inhibitor-induced hypertension and nephrotoxicity. The present study has found that low-dose aspirin (resulting in selective COX-1 inhibition and TXA₂ suppression) ameliorates TKI-induced hypertension, while high-dose aspirin (additionally resulting in COX-2 inhibition and PGI₂ suppression) prevents renal injury.