Antioxidant effect of doxycycline decreases MMP activity and blood pressure in SHR.

作者: Raquel C Antonio , Carla S Ceron , Elen Rizzi , Eduardo B Coelho , Jose E Tanus-Santos

DOI: 10.1007/S11010-013-1848-7

关键词:

摘要: Increased matrix metalloproteinase (MMP) levels are involved in vascular remodeling of hypertension. In this study, we hypothesized that doxycycline (a MMP inhibitor) could exert antioxidant effects, reverse establish remodeling, and lower blood pressure spontaneously hypertensive rats (SHR). SHR Wistar–Kyoto received either at 30 mg/kg/day by gavage or vehicle. Systolic (SBP) was assessed weekly tail cuff. After 5 weeks treatment, morphologic changes the aortic wall were studied hematoxylin/eosin sections. activity expression determined situ zymography using DQ gelatin immunofluorescence for MMP-2. Dihydroethidium used to evaluate reactive oxygen species (ROS) production fluorescence microscopy. Doxycycline reduced SBP 25 mmHg. However, antihypertensive effects not associated with significant reversal hypertension-induced hypertrophy. showed increased MMP-2 which co-localized higher ROS levels, all those biochemical alterations hypertension blunted treatment doxycycline. These results show inhibition established resulted gelatinolytic activity, remodeling.

参考文章(34)
SBA Cau, DA Guimaraes, E Rizzi, CS Ceron, LL Souza, CR Tirapelli, RF Gerlach, JE Tanus-Santos, Pyrrolidine dithiocarbamate down-regulates vascular matrix metalloproteinases and ameliorates vascular dysfunction and remodelling in renovascular hypertension. British Journal of Pharmacology. ,vol. 164, pp. 372- 381 ,(2011) , 10.1111/J.1476-5381.2011.01360.X
CS Ceron, MM Castro, E Rizzi, MF Montenegro, V Fontana, MCO Salgado, RF Gerlach, JE Tanus-Santos, Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase‐2 activity and expression in a model of renovascular hypertension British Journal of Pharmacology. ,vol. 160, pp. 77- 87 ,(2010) , 10.1111/J.1476-5381.2010.00678.X
Danielle A. Guimaraes, Elen Rizzi, Carla S. Ceron, Alisson M. Oliveira, Diogo M. Oliveira, Michele M. Castro, Carlos R. Tirapelli, Raquel F. Gerlach, Jose E. Tanus-Santos, Doxycycline dose-dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic & Clinical Pharmacology & Toxicology. ,vol. 108, pp. 318- 325 ,(2011) , 10.1111/J.1742-7843.2010.00656.X
Vanessa Fontana, Pamela S. Silva, Vanessa A. Belo, Raquel C. Antonio, Carla S. Ceron, Celso Biagi, Raquel F. Gerlach, Jose E. Tanus-Santos, Consistent Alterations of Circulating Matrix Metalloproteinases Levels in Untreated Hypertensives and in Spontaneously Hypertensive Rats: A Relevant Pharmacological Target Basic & Clinical Pharmacology & Toxicology. ,vol. 109, pp. 130- 137 ,(2011) , 10.1111/J.1742-7843.2011.00698.X
Michele M. Castro, Elen Rizzi, Lívia Figueiredo-Lopes, Karla Fernandes, Lusiane M. Bendhack, Dimitrius Leonardo Pitol, Raquel F. Gerlach, Jose E. Tanus-Santos, Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats. Atherosclerosis. ,vol. 198, pp. 320- 331 ,(2008) , 10.1016/J.ATHEROSCLEROSIS.2007.10.011
Li Hao, Min Du, Ana Lopez-Campistrous, Carlos Fernandez-Patron, Agonist-Induced Activation of Matrix Metalloproteinase-7 Promotes Vasoconstriction Through the Epidermal Growth Factor–Receptor Pathway Circulation Research. ,vol. 94, pp. 68- 76 ,(2004) , 10.1161/01.RES.0000109413.57726.91
Hui-Chin Lai, Yueh-Chiao Yeh, Chih-Tai Ting, Wen-Lieng Lee, Hsiao-Wei Lee, Li-Chuan Wang, Kuo-Yang Wang, Hui-Chun Lai, Angie Wu, Tsun-Jui Liu, Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts. European Journal of Pharmacology. ,vol. 644, pp. 176- 187 ,(2010) , 10.1016/J.EJPHAR.2010.07.010
Michele M. Castro, Elen Rizzi, Carla S. Ceron, Danielle A. Guimaraes, Gerson J. Rodrigues, Lusiane M. Bendhack, Raquel F. Gerlach, Jose Eduardo Tanus-Santos, Doxycycline ameliorates 2K-1C hypertension-induced vascular dysfunction in rats by attenuating oxidative stress and improving nitric oxide bioavailability. Nitric Oxide. ,vol. 26, pp. 162- 168 ,(2012) , 10.1016/J.NIOX.2012.01.009
Carla S. Ceron, Elen Rizzi, Danielle A. Guimaraes, Alisson Martins-Oliveira, Stefany B. Cau, Junia Ramos, Raquel F. Gerlach, Jose E. Tanus-Santos, Time course involvement of matrix metalloproteinases in the vascular alterations of renovascular hypertension. Matrix Biology. ,vol. 31, pp. 261- 270 ,(2012) , 10.1016/J.MATBIO.2012.01.009