Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension.
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.
Martinez
Marcio L L
ML
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
Lopes
Lívia F
LF
Coelho
Eduardo B
EB
Nobre
Fernando
F
Rocha
João B T
JB
Gerlach
Raquel F
RF
Tanus-Santos
Jose E
JE
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology*; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018592:Cross-Over Studies; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D016037:Single-Blind Method; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C060343:lercanidipine