Antihypertensive and antiremodeling effects of Rho kinase inhibition via activation of ACE2 pathway: support from studies in a human model opposite to hypertension.

摘要

The activation of Rho kinase (ROCK), the target of the GTPase RhoA, by vasopressors such as angiotensin II (Ang II) is an essential mechanism involved in changes of vascular tone and structure [1] leading to hypertension and cardiovascular remodeling [2,3]- It includes the modulation of myosin light chain phosphorylation through inhibition of myosin phosphatase, the contribution to the increase of Ca~(2+) sensitization in smooth muscle contraction, the downregulation of endothelial nitric oxide synthase (eNOS) and the control of the plasminogen activator inhibitor (PAI)-l production [1], whereas the inhibition of ROCK results in the suppression of neointimal formation and cardiovas- -cular hypertrophy, upregulation of nitric oxide system and may contribute to blood pressure (BP) reduction [1].