Combined rho kinase and renin–angiotensin system inhibition: a new therapeutic perspective for renal and cardiovascular remodeling

Diuretics prevent Rho-kinase activation and expression of profibrotic/oxidative genes in the hypertensive aortic wall

“…One novel intracellular mechanism that triggers vasoconstriction and cardiovascular remodeling is the small guanosine triphosphatase Rho and its target Rho-kinase (ROCK). Both enzymes have important roles in BP regulation, vascular smooth muscle contraction, and also in cardiovascular and renal remodeling [Jalil et al 2005[Jalil et al , 2010Shi and Wei, 2013;Loirand and Pacaud, 2010;Surma et al 2011;Satoh et al 2011;Shimokawa and Satoh, 2015].…”

“…Activated ROCK has an important role in mediating various cellular functions, such as vascular smooth muscle cell contraction, actin cytoskeleton organization, adhesion and motility, cytokinesis, and expression of genes involved in cardiovascular and renal remodeling. ROCK also mediates the upregulation of several proinflammatory, thrombogenic and fibrogenic molecules, and the downregulation of endothelial nitric oxide (NO) synthase (eNOS) [Jalil et al 2005[Jalil et al , 2010Shi and Wei, 2013;Loirand and Pacaud, 2010;Surma et al 2011;Satoh et al 2011;Shimokawa and Satoh, 2015]. Thus, when ROCK is activated, inflammation, thrombosis and tissue fibrosis are accelerated, whereas endothelial NO production is inhibited.…”