title: The alpha(1B)-adrenergic receptor decreases the inotropic response in the mouse Langendorff heart model.
abstract: OBJECTIVE
  alpha(1)-Adrenergic receptors (ARs) are known mediators of a positive inotropy in the heart, which may play even more important roles in heart disease. Due to a lack of sufficiently selective ligands, the contribution of each of the three alpha(1)-AR subtypes (alpha(1A), alpha(1B) and alpha(1D)) to cardiac function is not clearly defined. In this study, we used a systemically expressing mouse model that overexpresses the alpha(1B)-AR to define the role of this subtype in cardiac function.
  
  
  METHODS
  We used the mouse Langendorff heart model to assess changes in contractility under basal and phenylephrine-induced conditions.
  
  
  RESULTS
  We find that a 50% increase of the alpha(1B)-AR in the heart does not change basal cardiac parameters compared to age-matched normals (heart rate, +/-dP/dT and coronary flow). However, the inotropic response to phenylephrine is blunted. The same results were obtained in isolated adult myocytes. The difference in inotropy could be blocked by the selective alpha(1A)-AR antagonist, 5-methylurapidil, which correlated with decreases in alpha(1A)-AR density, suggesting that the alpha(1B)-AR had caused a compensatory downregulation of the alpha(1A)-AR.
  
  
  CONCLUSIONS
  These results suggest that the alpha(1B)-AR does not have a major role in the positive inotropic response in the mouse myocardium but may negatively modulate the response of the alpha(1A)-AR.
authors.affiliation: The Department of Molecular Cardiology NB50, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Ross
authors.forename: Boyd R
authors.initials: BR
authors.lastname: Rorabaugh
authors.forename: Dan
authors.initials: D
authors.lastname: Chalothorn
authors.forename: June
authors.initials: J
authors.lastname: Yun
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Gonzalez-Cabrera
authors.forename: Dan F
authors.initials: DF
authors.lastname: McCune
authors.forename: Michael T
authors.initials: MT
authors.lastname: Piascik
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Perez
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D010656:Phenylephrine