Doxycycline does not reverse structural observed in SHR aortas

Abstract

This study aimed at testing whether doxycycline (dox) would change the vascular structure, gelatinolytic activity and MMP‐2 levels in SHR aortas of 13‐week‐old animals treated for 5 weeks. SHR and Wistar‐Kyoto controls received either dox 30 mg/kg/day by gavage or vehicle. Systolic blood pressure (SBP) was assessed weekly by tail cuff, and at the end the aortas were processed for histological analysis and in situ zymography. Histological sections were used to determine media cross‐sectional area (CSA), media/lumen diameter (M/L), and the number of smooth muscle cells (SMC). Gelatinolytic activity was measured in situ using DQ gelatin. SBP was significantly lower in the SHR + doxy group compared to the SHR vehicle (P< 0.05). No changes were seen in any of the structural parameters (p>;0.05). Gelatinolytic activity was 3 times higher in the SHR aortic media (53.4 ± 15 units) compared with Wkyoto controls (18.2 to 18.9 ± 6 units), and dox treatment decreased the SHR values to 26.0 ±8 units (P <0.0001). Data confirms the high expression and activity of MMP‐2 in aortas of SHRs, and the effect of doxycycline in reversing the increase in SBP. However, at least for the time frame used (5 weeks) these changes were not concurrent with structural changes in the aortas, as shown in other models of hypertension after dox treatment.Support: State of Sao Paulo Research Foundation (FAPESP) and National (Brazilian) Research Council (CNPq).