Impact of Transient ACE Inhibition on Cardiac Reactive Oxygen Species Enzyme Expression in Response to Nitric Oxide Synthase Inhibition

Abstract

We have previously shown that transient treatment with the angiotensin converting enzyme (ACE) inhibitor, enalapril, protects against future nitric oxide synthase (NOS) inhibitor, Nw‐Nitro‐L‐arginine methyl‐ester (L‐NAME)‐induced pathological cardiac remodeling. This protection is characterized by reduced inflammation, fibrosis, and collagen deposition. ACE inhibitors have been shown to reduce oxidative stress, however whether long‐term changes in pro‐ or anti‐oxidant enzymes persist after cessation of treatment is not known. The purpose of this study was to examine the expression of pro‐ and anti‐oxidative enzymes to further examine their role in the cardiac protection conferred by transient ACE inhibition. Adult male spontaneously hypertensive rats (SHR) were divided into two groups with the control group (CL) receiving vehicle and the experimental group (EL) receiving enalapril (30 mg/kg per day) for two weeks, followed by a 2‐week washout. All rats were then treated with L‐NAME for 0 or 10 days. Pro‐oxidant enzyme NOX‐2 and anti‐oxidant enzymes SOD‐1, SOD‐2 and catalase levels were determined in left ventricle via Immuno‐Blotting. Two weeks after stopping enalapril, NOX‐2 levels tended to be increased over control. In response to L‐NAME, there was a significant increase in NOX‐2 in control (CL: 115%, p<0.05), but not EL (−4%, p>0.05) hearts over baseline control levels. Catalase, SOD‐1, and SOD‐2 levels were not persistently altered by transient ACE inhibition, nor were they affected by L‐NAME in either group. Taken together, the previously‐described long‐term protection afforded by transient ACE inhibition is not due to sustained up‐regulation of anti‐oxidant enzymes. Future studies will determine whether the lack of increase in NOX‐2 levels in the hearts of EL rats is a cause or consequence of the reduced fibrosis and inflammation.Support or Funding InformationSpringboard Grant, UA College of Medicine – PhoenixThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.