title: Endothelin-1 induces contraction of female rat internal pudendal and clitoral arteries through ET(A) receptor and rho-kinase activation.
abstract: BACKGROUND
  Endothelin-1 (ET-1), a potent vasoconstrictor peptide, acts mainly through the Gprotein-coupled ET(A) receptor (ET(A)R). Increased vascular ET-1 production and constrictor sensitivity have been observed in various cardiovascular diseases, including hypertension, as well as erectile dysfunction. The internal pudendal artery (IPA) supplies blood to the vagina and clitoris. Inadequate blood flow through the IPA may lead to insufficient vaginal engorgement and clitoral tumescence.
  
  
  OBJECTIVE
  Characterize the effects of ET-1 on the IPA and clitoral artery (CA).
  
  
  METHODS
  IPA and CA from female Sprague Dawley rats (225-250 g) were mounted in myograph chambers. Arterial segments were submitted to increasing concentrations of ET-1 (10-10-10-6 M). Segments were incubated with the ET(A)R antagonist, atrasentan (10-8 M) or the Rho-kinase inhibitor, Y-27632 (10-6 M) 30 minutes prior to agonist exposure. All E(max) values are expressed as % KCl-induced maximal contraction. ET(A)R, RhoA, and Rho-kinase expression from IPA was evaluated by Western blot. mRNA of preproET-1, ET(A)R, ET(B)R, RhoA, and Rho-kinase were measured by real time PCR.
  
  
  METHODS
  ET-1 constrictor sensitivity in IPA and CA, protein expression and messenger RNA levels of ET-1-mediated constriction components.
  
  
  RESULTS
  ET-1 concentration-dependently contracted IPA (% Contraction and pD2, respectively: 156 ± 18, 8.2 ± 0.1) and CA (163 ± 12, 8.8 ± 0.08), while ET(A)R antagonism reduced ET-1-mediated contraction (IPA: 104 ± 23, 6.4 ± 0.2; CA: 112 ± 17, 6.6 ± 0.08). Pretreatment with Y-27632 significantly shifted ET-1 pD2 in IPA (108 ± 24, 7.9 ± 0.1) and CA (147 ± 58 and 8.0 ± 0.25). Protein expression of ET(A)R, ET(B)R, RhoA, and Rho-kinase were detected in IPA. IPA and CA contained preproET-1, ET(A)R, ET(B)R, RhoA, and Rho-kinase message.
  
  
  CONCLUSIONS
  We observed that the IPA and CA are sensitive to ET-1, signaling through the ET(A)R and Rho-kinase pathway. These data indicate that ET-1 may play a role in vaginal and clitoral blood flow and may be important in pathologies where ET-1 levels are elevated.
authors.affiliation: Medical College of Georgia-Physiology, Augusta, GA, USA. Electronic address: kallahdadi@mcg.edu.
authors.forename: Kyan J
authors.initials: KJ
authors.lastname: Allahdadi
authors.affiliation: Medical College of Georgia-Physiology, Augusta, GA, USA.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Hannan
authors.affiliation: Medical College of Georgia-Physiology, Augusta, GA, USA; University of Sao Paulo-Pharmacology, Sao Paulo, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: University of Sao Paulo-Pharmacology, Sao Paulo, Brazil.
authors.forename: R Clinton
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology; D002987:Clitoris / Q000098:blood supply*; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014621:Vagina / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D054460:rho-Associated Kinases
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