title: Advanced-glycation end products (AGEs) derived from glycated albumin suppress early beta1-adrenergic preconditioning.
abstract: Ischemic heart disease in diabetic patients might be linked to the accumulation of advanced-glycation end products (AGEs). In ischemic rat hearts, expression of receptor for AGEs and its ligands is significantly enhanced and involved in cardiac ischemia/reperfusion (I/R) injury even in the absence of diabetes. It has recently been reported that diabetic human myocardium cannot be protected by preconditioning. In this context, our hypothesis was that beta1-adrenergic preconditioning might be altered in the presence of AGEs. Using an isolated non-working rat heart model, this study investigated the effect of AGEs on cardioprotection induced by transient beta1-adrenoceptor (beta1-AR) stimulation with xamoterol (Xa). After 6-hydroxydopamine (6-OHDA) pre-treatment and a 20-min stabilization period, hearts were perfused at constant pressure for 20 min, then subjected to 40 min of global ischemia and 30 min of reperfusion (I/R, Ctrl); and exposed to 0.01 microm Xa for 5 min framed with or without 15.2 microm albumin (Alb) or glycated albumin (Gly Alb). The main endpoints were the mean coronary flow (MCF), the left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and creatine kinase (CK) release and necrosis area. XA induced an increase in the MCF after I/R (t = 85 min), a protective effect on the LVEDP, an improvement in RPP, a decrease of CK release during reperfusion and a reduction of necrotic area. The beneficial effects induced by Xa during reperfusion were suppressed by the administration of Gly Alb during Xa infusion, whereas Alb did not hamper Xa-induced protection. These results suggest that AGEs suppress the cardioprotection resulting from the activation of beta1-ARs and thus might contribute to cardiovascular damages seen in diabetic patients.
authors.affiliation: Department of Pharmacology, Reims University Hospital, 51, rue Cognacq-Jay, 51095, Reims Cedex, France. arnaud.robinet@univ-reims.fr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Robinet
authors.forename: Loubna
authors.initials: L
authors.lastname: Alouane
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hoizey
authors.forename: Hervé
authors.initials: H
authors.lastname: Millart
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000494:pharmacology*; D017307:Xamoterol; D000093423:Glycated Serum Albumin
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000418:Albumins; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D017307:Xamoterol; D003402:Creatine Kinase; D000093423:Glycated Serum Albumin