ORIGINAL RESEARCH—BASIC SCIENCE: Intracavernosal Basic Fibroblast Growth Factor Improves Vasoreactivity in the Hypercholesterolemic Rabbit

Authors

  • Donghua Xie MD, PhD,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC, USA;
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  • Anne M. Pippen MS,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC, USA;
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  • Shelley I. Odronic BS,

    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC, USA;
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  • Brian H. Annex MD,

    Corresponding author
    1. Division of Cardiovascular Medicine and the Department of Medicine, Duke University Medical Center, Durham, NC, USA;
    2. Division of Cardiology and Department of Medicine, Durham VA Medical Center, Durham, NC, USA;
      Brian H. Annex, MD, 508 Foulton St., Box 111A, Durham, VA Medical Center, Durham, NC 27710, USA. Tel: (919) 286-0411 ext 7258; Fax: (919) 286-6861; E-mail: annex001@mc.duke.edu
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  • Craig F. Donatucci MD

    1. Department of Surgery, Duke University Medical Center, Durham, NC, USA
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Brian H. Annex, MD, 508 Foulton St., Box 111A, Durham, VA Medical Center, Durham, NC 27710, USA. Tel: (919) 286-0411 ext 7258; Fax: (919) 286-6861; E-mail: annex001@mc.duke.edu

ABSTRACT

Purpose.  We determined the effects of intracavernosal injection (ICI) of recombinant basic fibroblast growth factor (rbFGF) on corporal tissue in hypercholesterolemic rabbits.

Methods.  Twenty New Zealand White rabbits were fed a 1% cholesterol diet for 6 weeks and were randomly divided into four groups. Group 1 (N = 5) received an ICI of phosphate buffered saline solution (PBS) once and again 3 weeks later. Group 2 (N = 4) received an ICI of 2.5 µg rbFGF once and PBS 3 weeks later. Group 3 (N = 6) received an ICI of 2.5 µg rbFGF once and again 3 weeks later. Group 4 (N = 5) received an ICI of 2.5 µg rbFGF once. All animals were maintained on the high cholesterol diet until sacrifice, 3 weeks after last injection. Strips of corporal tissue were submaximally contracted with norepinephrine, and dose–response curves were generated to evaluate endothelial-dependent (acetylcholine, ACH) and endothelial-independent (sodium nitroprusside, SNP) vasoreactivity. Protein levels of bFGF and vascular endothelial growth factor (VEGF) were assessed by enzyme-linked immunosorbent assay. Neuronal nitric oxide synthase (nNOS) protein and mRNA were detected by Western blot and semi-quantitative polymerase chain reaction, respectively.

Results.  Vasoreactivity was improved by bFGF treatment as shown by higher ED50[−log(M)] of ACH and SNP in Groups 2, 3, and 4. The expression of bFGF protein, VEGF protein, nNOS protein, and mRNA were all increased after bFGF treatment.

Conclusions.  ICI of bFGF improved vasoreactivity in hypercholesterolemic rabbit corporal tissue, offering a new direction to explore for the treatment of erectile dysfunction. Xie D, Pippen AM, Odronic SI, Annex BH, and Donatucci CF. Intracavernosal basic fibroblast growth factor improves vasoreactivity in the hypercholesterolemic rabbit. J Sex Med 2006;3:223–232.

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