Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats
| Autor: | Raquel F. Gerlach, Jose E. Tanus-Santos, Lusiane M. Bendhack, Elen Rizzi, Caroline Demacq, Karla Fernandes, Marcio L.L. Martinez, Michele M. Castro |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Dihydropyridines medicine.medical_specialty Thiobarbituric acid medicine.drug_class Blood Pressure Calcium channel blocker medicine.disease_cause Thiobarbituric Acid Reactive Substances Muscle hypertrophy Renovascular hypertension chemistry.chemical_compound Internal medicine medicine Animals Rats Wistar Endothelial dysfunction Antihypertensive Agents Pharmacology Enzyme Precursors Reverse Transcriptase Polymerase Chain Reaction Lercanidipine Calcium Channel Blockers medicine.disease Rats Vasodilation Disease Models Animal Oxidative Stress Hypertension Renovascular Blood pressure Endocrinology chemistry Gelatinases Matrix Metalloproteinase 2 Oxidative stress medicine.drug |
| Zdroj: | European Journal of Pharmacology. 591:224-230 |
| ISSN: | 0014-2999 |
| Popis: | Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224+/-12 versus 183+/-11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P |
| Databáze: | OpenAIRE |
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