Increased Rho-Kinase Activity in Hypertensive Patients With Left Ventricular Hypertrophy

Abstract

There is experimental evidence on the role of Rho-kinase (ROCK) activation in cardiac hypertrophy but no information on its role in human hypertension and left ventricular hypertrophy (LVH). We hypothesized that ROCK activity is higher in hypertensive patients with LVH compared with hypertensive patients without LVH. We conducted a cross-sectional study comparing untreated hypertensive patients with (n = 41) and without LVH (n = 46) determined by echocardiography with a healthy normotensive control group (n = 51). Measurements included LV mass, dimensions, and function and ROCK activity determined in circulating leukocytes by measuring Western blot levels of phosphorylated to total myosin light chain phosphatase 1 (MYPT1-p/t). Compared with normotensive subjects, MYPT1-p/t was significantly increased by 4.5-fold in the hypertensive patients without LVH and by 9-fold in the hypertensive patients with LVH. Compared with the hypertension without LVH group, MYPT1-p/t was significantly increased by 2-fold in the hypertension with LVH gorup. In patients with eccentric LVH, the mean MYPT1-p/t ratio was significantly higher by 4-fold compared with hypertensive patients without eccentric LVH. Patients with an E/e' ratio ≥15 (n = 6) showed a higher MYPT1-p/t ratio (by 26%) compared with patients with a lower E/e' ratio (P ≤ 0.01). ROCK activity is higher in hypertensive patients with LVH compared with hypertensive patients without LVH, and it is further increased when eccentric LVH is present. Thus, in hypertension, ROCK activation is related to pathological cardiac remodeling and might have a role as an LVH marker.