| Title | Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine. | | Author(s) | Jacob-Ferreira AL, Palei AC, Cau SB, Moreno H, Martinez ML, Izidoro-Toledo TC, Gerlach RF, Tanus-Santos JE | | Institution | Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil. | | Source | Eur J Pharmacol 2009 Oct 29. | | Abstract | Nicotine plays a role in smoking-associated cardiovascular diseases, and may upregulate matrix metalloproteinase (MMP)-2 and MMP-9. We examined whether nicotine induces the release of MMP-2 and MMP-9 by rat smooth muscle cells (SMC), and whether doxycycline (non-selective MMP inhibitor) inhibits the vascular effects produced by nicotine. SMC were incubated with nicotine 0, 50, and 150 nM for 48h. MMP-2 and MMP-9 levels in the cells supernatants were determined by gelatin zymography. The acute changes in mean arterial pressure caused by nicotine 2mumol/kg (or saline) were assessed in rats pretreated with doxycycline (or saline). We also examined whether doxcycline (30mg/Kg, i.p., daily) modifies the effects of nicotine (10mg/kg/day; 4weeks) on the endothelium-dependent relaxations of rat aortic rings. Aortic MMP-2 levels were assessed by gelatin zymography. Aortic gelatinolytic activity was assessed using a gelatinolytic activity kit. MMP-2 and MMP-9 levels increased in the supernatant of SMC cells incubated with nicotine 150 nM (P<0.05) but not with 50 nM. Nicotine (2micromol/kg) produced lower increases in the mean arterial pressure in rats pretreated with doxycycline than those found in rats pretreated with saline (26+/-4 vs. 37+/-4mmHg, respectively; P<0.05). Nicotine impaired of the endothelium-dependent responses to acetylcholine, and treatment with doxycycline increased the potency (pD2) by approximately 25% (P<0.05). While we found no significant differences in aortic MMP-2 levels, nicotine significantly increased gelatinolytic activity (P<0.05). These findings suggest that nicotine produces cardiovascular effects involving MMPs. It is possible that MMPs inhibition may counteract the effects produced by nicotine. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19879865 |
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