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

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• 作者：Raquel C. Antonio (1)
  Carla S. Ceron (1)
  Elen Rizzi (1)
  Eduardo B. Coelho (2)
  Jose E. Tanus-Santos (1)
  Raquel F. Gerlach (3)
  
• 关键词：Hypertension ; SHR ; Doxycycline ; Oxidative stress ; MMPs
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：386
• 期：1-2
• 页码：99-105
• 全文大小：
• 作者单位：Raquel C. Antonio (1)
  Carla S. Ceron (1)
  Elen Rizzi (1)
  Eduardo B. Coelho (2)
  Jose E. Tanus-Santos (1)
  Raquel F. Gerlach (3)
  
  1. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto, SP, Brazil
  2. Department of Internal Medicine, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto, SP, Brazil
  3. Department of Morphology and Physiology, Dental School of Ribeirao Preto, University of So Paulo, Av. do Cafe S/N, Ribeiro Preto, SP, 14040-904, Brazil
  
• ISSN：1573-4919

文摘

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