The alpha(1B)-adrenergic receptor decreases the inotropic response in the mouse Langendorff heart model.
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.
Ross
Sean A
SA
The Department of Molecular Cardiology NB50, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Rorabaugh
Boyd R
BR
Chalothorn
Dan
D
Yun
June
J
Gonzalez-Cabrera
Pedro J
PJ
McCune
Dan F
DF
Piascik
Michael T
MT
Perez
Dianne M
DM
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
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D010656:Phenylephrine