Doxycycline Doseadependently Inhibits MMPa2aMediated Vascular Changes in 2K1C Hypertension

• Published in: Basic & clinical pharmacology & toxicology 2011-05, Vol.108 (5), p.318-325
• Main Authors: Guimaraes, Danielle A, Rizzi, Elen, Ceron, Carla S, Oliveira, Alisson M, Oliveira, Diogo M, Castro, Michele M, Tirapelli, Carlos R, Gerlach, Raquel F, TanusaSantos, Jose E
• Format: Article
• Language: English
• Subjects: Aorta; Blood pressure; Doxycycline; Gelatin; Gelatinase A; Hypertension; Hypertrophy; Matrix metalloproteinase; Microorganisms; Morphometry; Proteolysis; Vasodilation
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2010.00656.x

Hypertension induces vascular alterations that are associated with up-regulation of matrix metalloproteinases (MMPs). While these alterations may be blunted by doxycycline, a non-selective MMPs inhibitor, no previous study has examined the effects of different doses of doxycycline on these alterations. This is important because doxycycline has been used at sub-antimicrobial doses, and the use of lower doses may prevent the emergence of antibiotic-resistant microorganisms. We studied the effects of doxycycline at 3, 10 and 30mg/kg per day on the vascular alterations found in the rat two kidney-one clip (2K1C) hypertension (n=20 rats/group). Systolic blood pressure (SBP) was monitored during 4weeks of treatment. We assessed endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall was studied, and aortic MMP-2 levels/proteolytic activity were determined by gelatin and in situ zymography, respectively. All treatments attenuated the increases in SBP in hypertensive rats (195.4+/-3.9 versus 177.2+/-6.2, 176.3+/-4.5, and 173+/-5.1mmHg in 2K1C hypertensive rats treated with vehicle, or doxycycline at 3, 10, 30mg/kg per day, respectively (all p