Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive. The present study aimed to determine the role of endothelial mTORC1 in Ang II (angiotensin II)-induced hypertension and the underlying mechanism. Endothelial mTORC1 activity was increased by Ang II both in vitro and in vivo. Blood pressure was higher in Tie-2-Cre-mediated regulatory associated protein of mTOR (mammalian target of rapamycin; Raptor) heterozygous-deficient (Tie2Cre-Raptor(KD)) mice than control mice both before and after Ang II infusion. Acetylcholine-evoked endothelium-dependent relaxation of mesenteric arteries was impaired in Tie2Cre-Raptor(KD) mice. Treatment with indomethacin or a specific COX (cyclooxygenase)-2 inhibitor, NS-398, but not L-NG-nitroarginine methyl ester reduced endothelium-dependent relaxation in Raptor(flox/-) mice to a similar extent as in Tie2Cre-Raptor(KD) mice. Metabolomic profiling revealed that the plasma content of prostaglandin E-2 was reduced in Tie2Cre-Raptor(KD) mice with or without Ang II infusion. In endothelial cells, reduction of the protein level of YAP (yes-associated protein) with siRNA-mediated RPTOR deficiency was autophagy dependent and transcriptionally regulated the expression of COX-2 and mPGES-1 (microsomal prostaglandin E synthase-1). Hence, overexpression of YAP in endothelial cells enhanced the mRNA and protein levels of COX-2 and mPGES-1 and reversed the endothelial dysfunction and hypertension in Tie2Cre-Raptor(KD) mice. The present results demonstrate that suppression of mTORC1 activity in endothelial cells reduces prostaglandin E-2 production and causes hypertension by reducing YAP-mediated COX-2/mPGES-1 expression.