EDN1 and Hypertension: Rac1 is activated in response to a myriad of hypertrophic stimuli, including but not limited to angiotensin II (AngII), phenylephrine (PE) [27,28], endothelin-1 (ET-1) [28,29], stretch [30,31], pressure overload [6] and in multiple animal models of hypertension-induced heart disease [32,33].