title: Impaired endothelin calcium signaling coupled to endothelin type B receptors in penile arteries from insulin-resistant obese Zucker rats.
abstract: BACKGROUND
  Erectile dysfunction is considered as an early sign of subclinical vascular disease and endothelial dysfunction and a highly prevalent condition in diabetic patients.
  
  
  OBJECTIVE
  The current study assessed whether impaired vascular effects of endothelin (ET)-1 may contribute to the vascular dysfunction of penile arteries from a rat model of insulin resistance.
  
  
  METHODS
  The effect of ETA and ETB receptor antagonists was assessed on the intracellular Ca(2+) [Ca(2+) ]i and contractile responses to ET-1 in penile arteries from obese Zucker rats (OZR) and lean Zucker rats (LZR), and ET receptor expression in the arterial wall was assessed by immunohistochemistry.
  
  
  METHODS
  Changes in ET-1 [Ca(2+) ]i and vasoconstriction and ET receptor expression were evaluated in penile arteries from insulin-resistant rats.
  
  
  RESULTS
  ET-1-induced vasoconstriction was associated with a higher increase in smooth muscle [Ca(2+) ]i in penile arteries from OZR compared with LZR. Removal of the endothelium inhibited and enhanced contractions to the lowest and highest doses of ET-1, respectively, mainly in OZR. The selective ETA receptor antagonist BQ-123 inhibited ET-1 vasoconstriction and [Ca(2+) ]i response in both LZR and OZR. The ETB receptor antagonist BQ-788 had little effect in healthy arteries but markedly inhibited ET-1-induced increases in [Ca(2+) ]i and vasoconstriction in arteries from OZR. ETA receptors were located on the smooth muscle and endothelium of penile arteries, whereas ETB receptors were found on the arterial endothelium in LZR and OZR, and also on the smooth muscle in OZR, immunostaining for both receptors being higher in OZR.
  
  
  CONCLUSIONS
  Penile arteries from OZR exhibit an impaired ET-1 Ca(2+) signaling along with changes in the ET receptor profile. Thus, whereas ET-1 contraction and the associated [Ca(2+) ]i increase are mediated by smooth muscle ETA receptors in healthy arteries, ETB receptors contribute to contraction and are coupled to the augmented ET-1 [Ca(2+) ]i response under conditions of insulin resistance.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Contreras
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez
authors.forename: Belén
authors.initials: B
authors.lastname: Climent
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology; D020013:Calcium Signaling / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D018783:Impotence, Vasculogenic / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010413:Penis / Q000098:blood supply*; D051381:Rats; D011924:Rats, Zucker; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B
keywords: Calcium Signaling; ETA Receptor; ETB Receptor; Endothelial Dysfunction; Endothelin; Obese Zucker Rat; Penile Arteries