title: Reversal of hyperglycemic preconditioning by angiotensin II: role of calcium transport.
abstract: Myocardial cell death is an important contributor to the development of diabetic cardiomyopathy. It has been proposed that diabetes-mediated upregulation of the renin-angiotensin system leads to oxidative stress, the trigger for cardiomyocyte death and contractile dysfunction. However, the adverse effect of ANG II on the diabetic heart may extend beyond the development of the cardiomyopathy. ANG II also alters specific modulators of ischemic injury, such as PKC and calcium transport. Therefore, the present study examined the effect of ANG II on hyperglycemic preconditioning, a glucose-mediated condition associated with the elevation of PKC activity and alterations in calcium transport that render the cell resistant to hypoxia. Exposure of the glucose-treated cell to ANG II during the prehypoxic period blocked glucose-mediated cardioprotection. The reversal of hyperglycemic preconditioning was associated with enhanced accumulation of Ca(2+) during hypoxia, an effect prevented by inhibition of the Na(+)/ H(+) exchanger and the T-type Ca(2+) channel. The inhibitors of hypoxia-mediated Ca(2+) accumulation also blocked the reversal of hyperglycemic preconditioning by ANG II. Thus ANG II and glucose treatment exert opposite actions on the Na(+)/ H(+) exchanger and the T-type Ca(2+) channel. Because those transporters are involved in hypoxia-mediated apoptosis, they are logical candidates for the beneficial effects of high glucose and the adverse effects of ANG II on the hypoxic cardiomyocyte.
authors.affiliation: Dept. of Pharmacology, University of South Alabama College of Medicine, Mobile, AL 36688, USA.
authors.forename: Viktor
authors.initials: V
authors.lastname: Pastukh
authors.forename: Songwei
authors.initials: S
authors.lastname: Wu
authors.forename: Craig
authors.initials: C
authors.lastname: Ricci
authors.forename: Mahmood
authors.initials: M
authors.lastname: Mozaffari
authors.forename: Stephen
authors.initials: S
authors.lastname: Schaffer
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D020747:Calcium Channels, T-Type; D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005947:Glucose; D002118:Calcium