RESUMO

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Assuntos

Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Leucócitos/enzimologia , Quinases Associadas a rho/sangue , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Hipertensão/sangue , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/enzimologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fosfatase de Miosina-de-Cadeia-Leve/sangue , Ultrassonografia , Regulação para Cima , Rigidez Vascular , Função Ventricular Esquerda , Remodelação Ventricular

RESUMO

Introducción: La vía intracellular de RhoA/Rho kinasa es activada por agonistas de receptores acoplados a proteínas G pequeñas unidas a membrana. Su activación está relacionada al remodelado cardiovascular patológico. Previamente hemos observado aumento de actividad de Rho kinasa (ROCK) en pacientes con hipertensión arterial (HT) e hipertrofia ventricular izquierda como daño de órgano blanco. Pero su activación en relación a la diabetes no ha sido explorada en estos pacientes. Objetivo: Evaluar activación de Rho kinasa y parámetros de estrés oxidativo en pacientes hipertensos con diabetes tipo II (DMII). Métodos: Estudio comparativo entre pacientes con HT sin tratamiento, HT con DMII y hemoglobina glicosi-lada Alc > 7,5 por ciento y un grupo control normotenso. Se realizó ecocardiograma de superficie. Se midió activación de ROCK en leucocitos circulantes midiendo MYPT1 fosforilado/total (p/t) por Western blot y la velocidad de pulso carotídeo-femoral (PWV) para estimar distensibilidad arterial. El stress oxidativo se estimó midiendo ma-londialdehído (MDA) y 8-isoprostano (8-ISO) en suero. Resultados: Se incluyeron 21 pacientes hipertensos con DMII, 38 pacientes hipertensos sin DMII y 34 controles normotensos. La edad promedio fue 51 +/- 0,9; 48 +/- 0,9 y 52 (p: NS) +/- 1,1 y el 47 por ciento, 50 por ciento y 52 por ciento (p: NS) eran mujeres respectivamente. Los pacientes HT con DMII presentaron MYPTl p/t (5,6 +/- 1,3; 3,6 +/- 0,4; 2,1 +/- 0,1 p< 0,01), MDA (1,8 +/- 0,4/

Background: Rho/Rho-kinase intracellular pathway is activated by membrane bound small G-proteins. Activation of Rho/Rho-kinase pathway is related to pathologic cardiac remodeling. We have previously observed this activation (ROCK) in hypertensive patients with left ventricular hypertrophy. The influence of diabetes in this relationship has not been explored. Aim: to evaluate the activation of Rho-kinase and oxi-dative stress in hypertensive patients with type II diabetes (DMII). Methods: A comparative study between patients with untreated hypertension (HT), hypertensive patients with diabetes and hemoglobin A1c > 7.5 percent and normotensi-ve control subjects was performed. LVH was assessed by echocardiography. ROCK activity was measured in peripheral leukocytes by Western blot determination of phosphorilated / total MYPT1 ratio. Arterial compliance was determined by the relationship of carotid and femoral velocity signals (PWV) Oxidative stress was estimated by serum levels of malondialdehyde (MDA) and 8-isoprostane (8-ISO). Results: Hypertensives with DMII (n=21) had a mean age of 51 +/- 0.9 years, and 47 percent were females. Corresponding figures for 38 hypertensive patients without DM and 34 control patients were 48 ± 0,9 and 52 +/- 1,1 (NS) and 50 percent and 52 percent females, respectively (NS). The MYPT1 p/t ratio was 5,6 +/- 1,3; 3,6 +/- 0,4; 2,1 +/- 0,1 (p<0.01) in the 3 groups, respectively. MDA for the 3 groups was 1,8 +/- 0,4/

Assuntos

Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , /enzimologia , Hipertensão/enzimologia , Estresse Oxidativo , Quinases Associadas a rho/metabolismo , Análise de Variância , Pressão Arterial , Arteriosclerose , Western Blotting , Estudos Transversais , Ecocardiografia , Ativação Enzimática , Isoprostanos/análise , Malondialdeído/análise , Volume Sistólico