A Role for the ₁-Adrenergic Signalling Pathway in the Response of Papillary Muscles from Type 2 Diabetic Hearts to Anoxia-Reoxygenation

Authors: Barbara Huisamen¹; Jeanne Upton²; Amanda Lochner²

Source: Cardiovascular Drugs and Therapy, Volume 18, Number 4, July 2004 , pp. 247-255(9)

Publisher: Springer

Buy & download fulltext article:

Price: $47.00 plus tax (Refund Policy)

Abstract:

Hearts from animal models of type 2 diabetes present with abnormal contractility patterns. The role of altered alpha

₁-adrenergic signalling in this is not understood. In this study we report overexpression and altered regulation of alpha

₁-adrenergic receptors in two models of type 2 diabetic rat hearts. In combination with reduced contractile performance, papillary muscles from these hearts presented with an enhanced ability to react to alpha

₁-adrenergic stimulation. Concurrently, these muscles were protected against anoxia/reoxygenation induced damage. This protection could be abolished by pretreatment with the alpha

₁-adrenergic antagonist, prazosin. Overexpression of alpha

₁-adrenergic receptors may therefore be a two-edged sword: supplying a contractile reserve that can protect against anoxia/reoxygenation induced effects on inotropic ability on the one hand but also predisposing the hearts to elevated induction of intracellular Ca²⁺ release and possible arrhythmic effects on the other hand.

Keywords: alpha-adrenergic signalling; type 2 diabetes; myocardium; anoxia/reoxygenation; papillary muscle

Document Type: Research article

DOI: http://dx.doi.org/10.1023/B:CARD.0000041244.50971.ae

Affiliations: 1: MRC Diabetes & Heart Research Group, Department of Medical Physiology and Biochemistry, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, Republic of South Africa., Email: bh3@sun.ac.za 2: MRC Diabetes & Heart Research Group, Department of Medical Physiology and Biochemistry, Faculty of Health Sciences, University of Stellenbosch, P.O. Box 19063, Tygerberg 7505, Republic of South Africa

Publication date: 2004-07-01