title: Internal pudendal artery from type 2 diabetic female rats demonstrate elevated endothelin-1-mediated constriction.
abstract: BACKGROUND
  Diabetes is a risk factor for female sexual dysfunction (FSD). FSD has several etiologies, including a vasculogenic component that could be exacerbated in diabetes. The internal pudendal artery supplies blood to the vagina and clitoris and diabetes-associated functional abnormalities in this vascular bed may contribute to FSD.
  
  
  OBJECTIVE
  The Goto-Kakizaki (GK) rat is a non-obese model of type 2 diabetes with elevated endothelin-1 (ET-1) activity. We hypothesize that female GK rats have diminished sexual responses and that the internal pudendal arteries demonstrate increased ET-1 constrictor sensitivity.
  
  
  METHODS
  Female Wistar and GK rats were used. Apomorphine (APO)-mediated genital vasocongestive arousal (GVA) was measured. Functional contraction (ET-1 and phenylephrine) and relaxation (acetylcholine, ACh) in the presence or absence of the ETA receptor antagonist (ETA R; atrasentan) or Rho-kinase inhibitor (Y-27632) were assessed in the internal pudendal and mesenteric arteries. Protein expression of ET-1 and RhoA/Rho-kinase signaling pathway was determined in the internal pudendal and mesenteric arteries.
  
  
  METHODS
  APO-mediated GVAs; contraction and relaxation of internal pudendal and mesenteric arteries; ET-1/RhoA/Rho-kinase protein expression.
  
  
  RESULTS
  GK rats demonstrated no APO-induced GVAs. Internal pudendal arteries, but not mesenteric arteries, from GK rats exhibited greater contractile sensitivity to ET-1 compared with Wistar arteries. ETA R blockade reduced ET-1-mediated constriction in GK internal pudendal and mesenteric arteries. Rho-kinase inhibition reduced ET-1-mediated constriction of GK internal pudendal but not mesenteric arteries; however, it had no effect on arteries from Wistar rats. RhoA protein expression was elevated in GK internal pudendal arteries. At the highest concentrations, ACh-mediated relaxation was greater in the GK internal pudendal artery; however, no difference was observed in the mesenteric artery.
  
  
  CONCLUSIONS
  Female GK rats demonstrate decreased sexual responses that may be because of increased constrictor sensitivity to the ET-1/RhoA/Rho-kinase signaling in the internal pudendal artery.
authors: Department of Physiology, Georgia Health Sciences University, Augusta, GA 30912, USA. kyan_allahdadi@hotmail.com
authors: Kyan J
authors: KJ
authors: Allahdadi
authors: Johanna L
authors: JL
authors: Hannan
authors: Adviye
authors: A
authors: Ergul
authors: Rita C
authors: RC
authors: Tostes
authors: R Clinton
authors: RC
authors: Webb
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D019332:Endothelin-1 / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014621:Vagina / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D019332:Endothelin-1; D004958:Estradiol; D020742:rhoA GTP-Binding Protein; D001058:Apomorphine