Resumo

GABRIELLI, Luigi et al. Increased Rho-kinase activity in peripheral leukocytes is associated to oxidative stress and decreased compliance of the arterial wall in diabetic hypertensive patients. Rev Chil Cardiol [online]. 2011, vol.30, n.1, pp. 34-41. ISSN 0718-8560.  doi: 10.4067/S0718-85602011000100005.

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% 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% 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% and 52% 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/<M; 0,49 ± 0,08; 0,4± 0,06 (p < 0,01). The 8-isopros-tane levels were increased in diabetic hypertensives vs. the other groups. A similar difference was observed in PWV among groups (14 ± 0,9 m/sec; 11 ± 0,4; 8,1 ± 0,1). Conclusion: At comparable levels of left ventricular mass index, diabetic hypertensive patients had increased ROCK activity compared to non diabetic hypertensives. Also, compared to non-diabetic hypertensives and normotensive controls, diabetic hypertensive patients exhibited increased levels of oxidative stress. These findings correlated with a decreased arterial distensibility and may help explain the adverse vascular remodeling observed in hypertensive patients with DMII.