LAUSR

Introduction doxycycline (Dox) exerts important antioxidant effects and is able to chelate divalent metals present in the angiotensin-converting enzyme (ACE) structure that are essential for its activity. Increased ACE activity results in angiotensin (Ang) II formation that triggers oxidative stress in hypertension. In this way, we hypothesized that Dox inhibits ACE activity in hypertensive rats, reduces ROS production and ameliorates hypertension. Methods Sham-operated and 2K1C hypertensive rats were treated with Dox or water for 4 week. After treatment, two catheters were inserted into femoral artery or vein to record blood pressure and AngI infusion, respectively. Reactive oxygen species (ROS) were measured by lucigenin chemiluminescence and dihydroethidium oxidation in aortas. ACE activity was evaluated using a fluorescent substrate. To evaluate whether Dox inhibits ACE activity in vitro, aortic tissues from 2K1C rats were incubated with Dox or captopril. To evaluate acute Dox effects in vivo AngI was infused after single administration of Dox or saline in normotensive rats. Data were considered significant when p Results Dox treatment reduced 21% the SBP in 2K1C rats (p Conclusion Chronic treatment with Dox inhibited ACE activity in aorta of 2K1C rats and contributed to the reduction of SBP and ROS formation. The mechanism by which Dox inhibits ACE activity was not dependent of metal chelation and needs further investigation.