C3H Mice are Resistant to Hypertensive Renovascular Remodeling Due to Decreased Mitochondrial Oxidative Stress

Abstract

Increased reactive oxygen species (ROS) has been implicated as a causative factor in angiotensin‐II (Ang‐II) induced hypertension. Sirtuin‐3 (SIRT3) is a mitochondrial protein involved in the regulation of micothondrial ROS. In earlier studies, we found that C3H mice develop mild hypertension and show decreased renal remodeling to pressor dose of Ang‐II. In this study, we hypothesized that C3H mice show decreased susceptibility to hypertension due to SIRT3 modulation of mitochondrial ROS production and by decreasing inflammation. Wildtype (WT) and C3H/HeJ mice were implanted with osmotic pumps loaded without or with Angiotensin‐II (Ang‐II) for delivery at 250 ng/kg/min. Mitochondrial oxidative stress was measured as H2O2 production. Ang‐II administration increased H2O2 in WT mice more than in C3H. Higher levels of SIRT3 and decreased levels of TNF alpha and IL‐6 was found in C3H+Ang‐II mice compared to WT+Ang‐II. C3H+AngII mice also showed decreased levels of MMP‐9 and activity compared to WT+Ang‐II. Vascular staining for collagen revealed decreased type‐1 and −III collagen in C3H mice indicating decreased fibrosis. We conclude that in C3H mice, SIRT3 modulation maintains mitochondrial homeostasis, reduces inflammation and protects the kidney from adverse effects of hypertension.