A role for the alpha1-adrenergic signalling pathway in the response of papillary muscles from type 2 diabetic hearts to anoxia-reoxygenation

Cardiovascular Drugs and Therapy
Barbara HuisamenAmanda Lochner

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 Ca(2+) release and possible arrhythmic effects on the other hand.

Citations

Jul 24, 2021·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Alexey S AverinOlga V Nakipova

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