title: C-type natriuretic peptide hyperpolarizes and relaxes human penile resistance arteries.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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 factor(4-23) (cANF(4-23)), induced relaxations with less maximum response compared to CNP.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;; Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Kun
authors.affiliation: Department of Urology, University of Szeged, Szeged, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Kiraly
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Pataricza
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Marton
authors.affiliation: Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Iren
authors.initials: I
authors.lastname: Krassoi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;; Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Varro
authors.affiliation: Department of Pharmacology, University of Aarhus, Aarhus, Denmark. Electronic address: us@farm.au.dk.
authors.forename: Ulf
authors.initials: U
authors.lastname: Simonsen
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary;; Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Julius Gy
authors.initials: JG
authors.lastname: Papp
authors.affiliation: Department of Urology, University of Szeged, Szeged, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pajor
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D017609:Barium Compounds / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D045283:Natriuretic Agents / Q000494:pharmacology*; D020098:Natriuretic Peptide, C-Type / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010413:Penis / Q000098:blood supply*; D010455:Peptides / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D045283:Natriuretic Agents; D009498:Neurotoxins; D010455:Peptides; D014665:Vasodilator Agents; C024986:barium chloride; D018999:Charybdotoxin; D020098:Natriuretic Peptide, C-Type; D019335:Nitroarginine; D001030:Apamin; D010042:Ouabain; C064719:iberiotoxin; D000109:Acetylcholine; D007213:Indomethacin