Comparison of Candesartan and Angiotensin-(1-7) Combination and Mito Tempo Treatment for Normalizing Blood Pressure and Sympathovagal Balance in (Mren2)27 Rats.

Hypertensive transgenic (mRen2)27 rats exhibit impaired baroreflex sensitivity (BRS) for control of heart rate (HR). Intracerebroventricular (ICV) infusion of Ang-(1-7) improves indices of vagal BRS independent of lowering mean arterial pressure (MAP), while AT1 receptor blockade normalizes MAP and indices of sympathetic tone without correcting the vagal BRS. Scavenging cellular reactive oxygen species (ROS) with tempol in brain fails to correct either hypertension or sympathovagal balance in these animals, despite reports that mitochondrial ROS contributes to Ang II-infusion hypertension. To examine effects of a putative preferential mitochondrial ROS scavenger in the brain of (mRen2)27 rats, ICV infusions of Mito-TEMPO (3.2 μg/2.5 μL/h) were compared with artificial cerebrospinal fluid (aCSF; 2.5 μL/h) and combination AT1 receptor antagonist candesartan (CAN: 4 μg/2.5 μL/h) plus Ang-(1-7) (.1 μg/2.5μL/h) treatment. MAP was lower following CAN+Ang-(1-7) treatment and both vagal and sympathetic components of BRS and sympathovagal balance were improved. In contrast, Mito-TEMPO improved sympathetic components of BRS, and tended to improve overall sympathovagal balance, but failed to alter MAP in this model of hypertension. While further studies are required to determine whether Mito-TEMPO or CAN+Ang-(1-7) treatment at the doses used altered mitochondrial ROS, optimal therapeutic benefits are achieved by shifting the balance from Ang II towards Ang-(1-7) in this model of chronic RAS-dependent hypertension.