A role for the alpha1-adrenergic signalling pathway in the response of papillary muscles from type 2 diabetic hearts to anoxia-reoxygenation.
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.
Huisamen
Barbara
B
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. bh3@sun.ac.za
Upton
Jeanne
J
Lochner
Amanda
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015415:Biomarkers; D001786:Blood Glucose; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011224:Prazosin