Peer-review started: June 18, 2015
First decision: July 31, 2015
Revised: November 16, 2015
Accepted: December 3, 2015
Article in press: December 4, 2015
Published online: February 23, 2016
Asymptomatic organ damage due to progressive kidney damage, cardiac hypertrophy and remodeling put hypertensive patients at high risk for developing heart and renal failure, myocardial infarction and stroke. Current antihypertensive treatment normalizes high blood pressure, partially reverses organ damage, and reduces the incidence of heart and renal failure. Activation of the renin-angiotensin system (RAS) is a primary mechanism of progressive organ damage and, specifically, a major cause of both renal and cardiovascular fibrosis. Currently, inhibition of the RAS system [mainly with angiotensin I converting enzyme inhibitors or angiotensin II (Ang II) receptor antagonists] is the most effective antihypertensive strategy for normalizing blood pressure and preventing target organ damage. However, residual organ damage and consequently high risk for cardiovascular events and renal failure still persist. Accordingly, in hypertension, it is relevant to develop new therapeutic perspectives, beyond reducing blood pressure to further prevent/reduce target organ damage by acting on pathways that trigger and maintain cardiovascular and renal remodeling. We review here relevant novel mechanisms of target organ damage in hypertension, their role and evidence in prevention/regression of cardiovascular remodeling and their possible clinical impact as well. Specifically, we focus on the signaling pathway RhoA/Rho kinase, on the impact of the vasodilatory peptides from the RAS and some insights on the role of estrogens and myocardial chymase in cardiovascular hypertensive remodeling.
Core tip: Antihypertensive treatment normalizes high blood pressure, partially reverses organ damage, and reduces the incidence of heart and renal failure. However, residual organ damage and high risk for cardiovascular events still persist. We review here novel relevant mechanisms of cardiovascular damage in hypertension, their role and evidence in prevention/regression of cardiovascular remodeling and their possible clinical impact. We focus on the signaling pathway RhoA/Rho kinase, on the impact of the vasodilatory peptides from the renin angiotensin system and some insights on the role of estrogens and myocardial chymase in cardiovascular remodeling due to hypertension.