The α1B-adrenergic receptor decreases the inotropic response in the mouse Langendorff heart model

Sean A. Ross, Boyd R. Rorabaugh, Dan Chalothorn, June Yun, Pedro J. Gonzalez-Cabrera, Dan F. McCune, Michael T. Piascik, Dianne M. Perez

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Objective: α1-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 α1-AR subtypes (α1A, α1B and α1D) to cardiac function is not clearly defined. In this study, we used a systemically expressing mouse model that overexpresses the α1B-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 α1B-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 α1A-AR antagonist, 5-methylurapidil, which correlated with decreases in α1A-AR density, suggesting that the α1B-AR had caused a compensatory downregulation of the α1A-AR. Conclusions: These results suggest that the α1B-AR does not have a major role in the positive inotropic response in the mouse myocardium but may negatively modulate the response of the α1A-AR.

Original languageEnglish
Pages (from-to)598-607
Number of pages10
JournalCardiovascular Research
Volume60
Issue number3
DOIs
StatePublished - Dec 1 2003

Bibliographical note

Funding Information:
This work was funded by RO1HL614380-04 (DMP), R01HL 31820-11(MTP), a local American Heart Association fellowship to SAR, PJG-C and DC, an NRSA to (DFM) and a T32 HL07914 training grant in Vascular Cell Biology to BR and JY.

Keywords

  • Adrenergic receptor
  • Heart
  • Inotropy
  • Myocyte

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'The α1B-adrenergic receptor decreases the inotropic response in the mouse Langendorff heart model'. Together they form a unique fingerprint.

Cite this