Abstract
BACKGROUND: Rho-associated kinases (ROCKs) play an important role in Ca sensitization and vascular resistance. Activation of ROCKs is associated with hypertension. The purpose of this study was to evaluate the effect of the calcium channel blocker amlodipine on ROCKs activity in patients with hypertension. METHODS: We evaluated ROCK activity in peripheral leukocytes by Western blot analysis in 651 patients with hypertension treated with antihypertensive agents, 28 untreated hypertensive patients and 28 healthy individuals, and the effects of treatment with amlodipine or losartan for 12 weeks on ROCK activity in 28 untreated hypertensive patients who were randomly divided into an amlodipine group (n = 14) and a losartan group (n = 14). ROCK activity was defined as the ratio of phospho myosin-binding subunit (MBS) on myosin light-chain phosphatase to total MBS. RESULTS: Leukocyte ROCK activity was greater in untreated patients with essential hypertension than in the healthy individuals (0.84 ± 0.24 vs. 0.61 ± 0.18, P = 0.03). In 651 patients with hypertension treated with antihypertensive agents, ROCK activity was significantly lower in the calcium channel blocker-treated group than in the groups treated with renin-angiotensin system inhibitors, diuretics, and β-blockers (0.70 ± 0.24 vs. 0.85 ± 0.29, 0.83 ± 0.24, and 0.86 ± 0.31, P < 0.05, respectively). ROCK activity after 4 and 12 weeks of treatment was significantly decreased in the amlodipine group (0 weeks: 0.85 ± 0.25, 4 weeks: 0.66 ± 0.16, 12 weeks: 0.64 ± 0.15, P < 0.05, respectively) but not in the losartan group, whereas the antihypertensive effects were similar in the two groups. CONCLUSION: These findings suggest that calcium channel blocker amlodipine inhibits ROCK activity in patients with hypertension.