Exercise prevents Western diet-associated erectile dysfunction and coronary artery endothelial dysfunction: response to acute apocynin and sepiapterin treatment

Am J Physiol Regul Integr Comp Physiol. 2013 Aug 15;305(4):R423-34. doi: 10.1152/ajpregu.00049.2013. Epub 2013 Jun 12.


The aim of this study was to investigate aerobic exercise training as a means to prevent erectile dysfunction (ED) and coronary artery disease (CAD) development associated with inactivity and diet-induced obesity. Male Sprague-Dawley rats were fed a Western diet (WD) or a control diet (CD) for 12 wk. Subgroups within each diet remained sedentary (Sed) or participated in aerobic interval treadmill running throughout the dietary intervention. Erectile function was evaluated under anesthesia by measuring the mean arterial pressure and intracavernosal pressure in response to electrical field stimulation of the cavernosal nerve, in the absence or presence of either apocynin, an NADPH oxidase inhibitor, or sepiapterin, a tetrahydrobiopterin precursor. Coronary artery endothelial function (CAEF) was evaluated ex vivo with cumulative doses of ACh applied to preconstricted segments of the left anterior descending coronary artery. CAEF was assessed in the absence or presence of apocynin or sepiapterin. Erectile function (P < 0.0001) and CAEF (P < 0.001) were attenuated in WD-Sed. Exercise preserved erectile function (P < 0.0001) and CAEF (P < 0.05) within the WD. Erectile function (P < 0.01) and CAEF (P < 0.05) were augmented by apocynin only in WD-Sed, while sepiapterin (P < 0.05) only augmented erectile function in WD-Sed. These data demonstrate that a chronic WD induces impairment in erectile function and CAEF that are commonly partially reversible by apocynin, whereas sepiapterin treatment exerted differential functional effects between the two vascular beds. Furthermore, exercise training may be a practical means of preventing diet-induced ED and CAD development.

Keywords: NADPH oxidase; diet-induced obesity; endothelial nitric oxide synthase uncoupling; high-fat high-sucrose; high-intensity interval training.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Biopterin / analogs & derivatives
  • Biopterin / metabolism
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / prevention & control*
  • Coronary Vessels / drug effects*
  • Coronary Vessels / metabolism
  • Coronary Vessels / physiopathology
  • Diet, High-Fat*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Enzyme Inhibitors / pharmacology*
  • Erectile Dysfunction / etiology
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / physiopathology
  • Erectile Dysfunction / prevention & control*
  • Exercise Therapy* / methods
  • Male
  • NADPH Oxidases / metabolism
  • Obesity / etiology
  • Obesity / physiopathology
  • Oxidative Stress / drug effects
  • Penile Erection / drug effects*
  • Pterins / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sedentary Behavior
  • Time Factors
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology


  • Acetophenones
  • Enzyme Inhibitors
  • Pterins
  • Vasodilator Agents
  • Biopterin
  • acetovanillone
  • sepiapterin
  • NADPH Oxidases
  • sapropterin