EDN1 and Hypertension: There are several proposed mechanisms for VSP inhibitor-associated hypertension: reduction in nitric oxide (NO) production, increased expression of pro-hypertensive agents such as endothelin-1 (ET-1), microvascular rarefaction, activation of renin-angiotensin system, oxidative stress, pressure-natriuresis system, mechanical properties of large vessels (arterial stiffness).