Increased rho-kinase activity in hypertensive patients with left ventricular hypertrophy.

The small guanosine triphosphatase Rho and its target Rhokinase (ROCK) play significant roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein (such as angiotensin II, endothelin, or noradrenalin), by growth factors, or by cytokines.1–4 Once Rho is activated, it translocates to the cell membrane where it activates ROCK. Then ROCK phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation, and cell migration. In this way, Rho and ROCK activation have important effects on several cardiovascular diseases.2–6 Additionally, there is experimental evidence on the significant role of ROCK activation in the development of cardiac hypertrophy, remodeling, and ventricular dysfunction. In Dahl salt-sensitive hypertensive rats, increased left ventricular weight was significantly ameliorated by using the ROCK inhibitor Y-276327.7Upregulated RhoA protein, ROCK gene expression, and myosin lightchain phosphorylation in the hypertrophy stage were also suppressed by the ROCK inhibitor.7 In hypertensive rats, the ROCK inhibitor fasudil attenuated myocardial fibrosis possibly through suppression of monocyte/macrophage infiltration of the heart.8 Moreover, ROCK is significantly activated in the aortic wall in normotensive rats with genetically high angiotensin I–converting enzyme and angiotensin II, and it causes activation of genes that promote vascular remodeling, such as monocyte chemoattractant protein 1, transforming growth factor β1, and plasminogen activator inhibitor 1, and also increases vascular oxidative stress.9 In Dahl salt-sensitive hypertensive Increased Rho-Kinase Activity in Hypertensive Patients With Left Ventricular Hypertrophy