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

Raquel C Antonio1, Carla S Ceron, Elen Rizzi

  • 1Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto, SP, Brazil.

Molecular and Cellular Biochemistry
|October 12, 2013
PubMed

Insights

Doxycycline, an MMP inhibitor, lowered blood pressure in hypertensive rats by reducing oxidative stress and MMP activity. However, it did not reverse hypertension-induced vascular remodeling.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Biochemistry

Background:

  • Elevated matrix metalloproteinase (MMP) levels contribute to vascular remodeling in hypertension.
  • Hypertension is characterized by vascular hypertrophy and increased oxidative stress.

Purpose of the Study:

  • To investigate the effects of doxycycline, an MMP inhibitor, on blood pressure, vascular remodeling, and oxidative stress in spontaneously hypertensive rats (SHR).
  • To determine if doxycycline can reverse established hypertension-induced vascular changes.

Main Methods:

  • Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were treated with doxycycline (30 mg/kg/day) or vehicle for 5 weeks.
  • Systolic blood pressure (SBP) was monitored weekly.
  • Aortic MMP activity, MMP-2 expression, and reactive oxygen species (ROS) production were assessed using in situ zymography, immunofluorescence, and dihydroethidium staining, respectively.
  • Vascular morphology was examined via hematoxylin and eosin staining.

Main Results:

  • Doxycycline treatment significantly reduced SBP by 25 mmHg in SHR.
  • While doxycycline blunted increased aortic MMP-2 levels, MMP activity, and ROS production, it did not significantly reverse hypertension-induced vascular hypertrophy.
  • The antihypertensive effect of doxycycline was not associated with reversal of vascular remodeling.

Conclusions:

  • MMP inhibition with doxycycline in established hypertension exerts antioxidant effects and lowers blood pressure.
  • Doxycycline reduces gelatinolytic activity and oxidative stress in hypertensive rats.
  • The antihypertensive effects of doxycycline in SHR are not linked to the reversal of vascular remodeling.

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