Erectile Dysfunction Precedes Coronary Artery Endothelial Dysfunction in Rats Fed a High-Fat, High-Sucrose, Western Pattern Diet

Authors

  • Justin D. La Favor MS,

    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    2. Department of Kinesiology, East Carolina University, Greenville, NC, USA
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  • Ethan J. Anderson PhD,

    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    2. Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
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  • Robert C. Hickner PhD,

    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    2. Department of Kinesiology, East Carolina University, Greenville, NC, USA
    3. Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
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  • Christopher J. Wingard PhD

    Corresponding author
    1. East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA
    2. Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA
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Christopher J. Wingard, PhD, Department of Physiology, Brody School of Medicine at East Carolina University, 600 Moye Blvd., 6N-98, Greenville, NC 27834, USA. Tel: (252) 744-2804; Fax: (252) 744-3650; E-mail: wingardc@ecu.edu

ABSTRACT

Introduction.  It is suggested that erectile dysfunction (ED) may be an early risk factor for cardiovascular disease.

Aim.  The goal of this study was to determine whether development of ED precedes the onset of coronary artery endothelial dysfunction in response to a Western diet (WD), thereby establishing whether the WD differentially impacts the endothelium in a time-dependent manner. Additionally, a goal was to determine if diet-induced ED is reversible with intracavernosal sepiapterin treatment.

Methods.  Male Sprague-Dawley rats were fed a WD for 4, 8, or 12 weeks, or a control diet for 8 weeks. Erectile function was evaluated by measuring the mean arterial pressure (MAP) and intracavernosal pressure (ICP) in response to electrical field stimulation of the cavernosal nerve near the major pelvic ganglion, in the absence and presence of sepiapterin. Coronary artery endothelial function was evaluated ex vivo with cumulative doses of acetylcholine (ACh) applied to segments of the left anterior descending coronary artery preconstricted with serotonin.

Main Outcome Measures.  Erectile function was assessed as the ICP response to electrical field stimulation (EFS), normalized to MAP. Coronary artery endothelial function was assessed as the effective concentration producing 50% of a maximal response (EC50) of the ACh response.

Results.  The ICP/MAP response to EFS was significantly attenuated following both 8 and 12 weeks of the WD compared with the control diet (P < 0.05). Sepiapterin treatment augmented the ICP/MAP response in all WD groups (P < 0.05). The coronary artery EC50 of the ACh response was not different from control following 4 or 8 weeks but was significantly elevated following 12 weeks of the WD (P < 0.01).

Conclusions.  These data suggest that erectile function is reduced prior to coronary artery endothelial function in response to the WD. Improvement of erectile function with sepiapterin in WD rats indicates that nitric oxide synthase uncoupling is a key mechanism in diet-induced ED. La Favor JD, Anderson EJ, Hickner RC, and Wingard CJ. Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed a high-fat, high-sucrose, Western pattern diet. J Sex Med 2013;10:694–703.

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