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 a...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 Rho A/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.展开更多
基金Supported by Comisión Nacional de Investigación Científicay Tecnológica(CONICYT,Chile)grants FONDECYT 1121060(to JEJ and MPO),FONDEF D11I1122(to MPO and JEJ)and FONDAP 15130011(to MPO)
文摘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 Rho A/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.
