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C-Type Natriuretic Peptide Hyperpolarizes and Relaxes Human Penile Resistance Arteries

Authors

  • Attila Kun PhD,

    1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
    2. Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary;
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    • 1

      Present address: Department of Pharmacology, University of Aarhus, Aarhus, Denmark.

  • Istvan Kiraly MD,

    1. Department of Urology, University of Szeged, Szeged, Hungary;
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  • Janos Pataricza MD, PhD,

    1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
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  • Zoltan Marton BSc,

    1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
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  • Iren Krassoi BSc,

    1. Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary;
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  • Andras Varro MD, PhD, DSc,

    1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
    2. Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary;
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  • Ulf Simonsen MD, PhD,

    Corresponding author
    1. Department of Pharmacology, University of Aarhus, Aarhus, Denmark
      Professor Ulf Simonsen, MD, PhD, Faculty of Health Sciences, Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark. Tel: +4589421713; Fax: +4586128804; E-mail: us@farm.au.dk
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  • Julius Gy. Papp MD, PhD, DSc,

    1. Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;
    2. Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary;
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  • Laszlo Pajor MD, PhD

    1. Department of Urology, University of Szeged, Szeged, Hungary;
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Professor Ulf Simonsen, MD, PhD, Faculty of Health Sciences, Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark. Tel: +4589421713; Fax: +4586128804; E-mail: us@farm.au.dk

ABSTRACT

Introduction.  In addition to nitric oxide (NO), it is thought that an endothelium-derived hyperpolarizing factor (EDHF) plays an important role in the relaxation of penile arteries. Recently, it has been shown that C-type natriuretic peptide (CNP) shows the characteristics of EDHF in systemic small arteries.

Aim.  To investigate the mechanism involved in CNP-evoked vasodilatation and to address whether CNP is an EDHF in human penile resistance arteries.

Methods.  Erectile tissue was obtained in connection with transsexual operations. Intracavernous penile resistance arteries were isolated and mounted in microvascular myographs for recording of isometric tension. Membrane potential was recorded by the use of a small glass electrode inserted in the smooth muscle layer.

Main Outcome Measure.  In vitro evidence for hyperpolarization and vasorelaxation induced by CNP.

Results.  Acetylcholine (ACh) and CNP hyperpolarized smooth muscle membrane potential in resting penile resistance arteries. In penile small arteries incubated with inhibitors of NO synthase and cyclooxygenase and contracted with phenylephrine, ACh and CNP evoked concentration-dependent relaxations with maximum of 56 ± 6% and 71 ± 6%, respectively. Addition of a combination of blockers of small- and intermediate-conductance calcium-activated K+ channels, apamin plus charybdotoxin, respectively, and a combination thought to block the smooth muscle response of EDHF-type relaxation, barium plus ouabain, markedly reduced ACh- and CNP-evoked relaxation. Iberiotoxin, a blocker of big-conductance calcium-activated K+ channels inhibited the vasorelaxant responses evoked by ACh and CNP. A selective natriuretic peptide receptor type C (NPR-C) agonist, C-atrial natriuretic factor4-23 (cANF4-23), induced relaxations with less maximum response compared to CNP.

Conclusion.  The present findings suggest that CNP possesses the characteristics of an EDHF in human penile resistance arteries. By activation of natriuretic peptide receptor type B and NPR-C receptors, CNP causes relaxation by activation, respectively, of large-conductance calcium-activated K+ channels and Na+/K+-adenosine triphosphatase (ATPase), and barium-sensitive inward rectifier K+ channels. Modulation of the CNP pathway opens for new treatment modalities of erectile dysfunction. Kun A, Kiraly I, Pataricza J, Marton Z, Krassoi I, Varro A, Simonsen U, Gy. Papp J, and Pajor L. C-type natriuretic peptide hyperpolarizes and relaxes human penile resistance arteries. J Sex Med 2008;5:1114–1125.

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