Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension.

Abstract

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.

• Authors: Marcio L L Martinez, Lívia F Lopes, Eduardo B Coelho, Fernando Nobre, João B T Rocha, Raquel F Gerlach, Jose E Tanus-Santos
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 47 Issue 1 Pg. 117-22 (Jan 2006) ISSN: 0160-2446 [Print] United States
• PMID: 16424795 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Calcium Channel Blockers
• Dihydropyridines
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• lercanidipine

Topics

• Adult
• Aged
• Antihypertensive Agents (pharmacology)
• Blood Pressure Monitoring, Ambulatory
• Calcium Channel Blockers (pharmacology)
• Cross-Over Studies
• Dihydropyridines (pharmacology)
• Female
• Humans
• Hypertension (drug therapy, enzymology)
• Male
• Matrix Metalloproteinase 2 (blood)
• Matrix Metalloproteinase 9 (blood, drug effects)
• Middle Aged
• Oxidative Stress (drug effects)
• Single-Blind Method
• Tissue Inhibitor of Metalloproteinase-1 (blood)