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Lercanidipine Reduces Matrix Metalloproteinase-9 Activity in Patients With Hypertension

2006; Lippincott Williams & Wilkins; Volume: 47; Issue: 1 Linguagem: Inglês

10.1097/01.fjc.0000196241.96759.71

1533-4023

Marcio L.L. Martinez, Lucia Rossetti Lopes, Eduardo Barbosa Coelho, Fernando Nobre, João Batista Teixeira da Rocha, Raquel F. Gerlach, José E. Tanus‐Santos,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

Increased levels of metalloproteinase (MMP)-9 have been shown in hypertensive patients. Lercanidipine is a calcium channel blocker with antioxidant actions. We examined whether lercanidipine produces antioxidant effects and reduces MMP-9 activity in hypertensive patients in a placebo-controlled, crossover, single-blinded design study including 18 healthy volunteers (control group), and 14 hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus. Hypertensive patients were randomized to treatment with placebo (15 days) or lercanidipine 20 mg/d (15 days). Arterial blood pressure was evaluated with ambulatory blood pressure monitoring. Plasma thiobarbituric acid reactive species (TBA-RS) levels were measured to assess oxidative stress, and plasma MMP-2 and MMP-9 were assayed by gel zymography before and after treatment with placebo or lercanidipine. Plasma concentrations of tissue inhibitor of metalloproteinases (TIMP)-1 were measured by ELISA. Lercanidipine reduced mean arterial pressure by 7% in hypertensive patients without diabetes (P < 0.05), but not in hypertensive patients with diabetes. It significantly decreased plasma TBA-RS levels in hypertensive patients without and with diabetes (95% confidence interval [CI], −26 to −46%, P = 0.048, and −22 to −33%, P = 0.036, respectively). In addition, lercanidipine decreased activated MMP-9 in hypertensive patients without and with diabetes (95% CI, −19 to −47%, P = 0.047, and −80 to −96%, P = 0.010, respectively). No effects were seen on MMP-2. No significant differences or changes in plasma TIMP-1 concentrations were found. Therefore, we demonstrate for the first time that lercanidipine consistently decreased MMP-9 activity and reduced oxidative stress in hypertensive patients, thus suggesting a mechanism probably involved in the pleotropic actions of lercanidipine.