title: Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia-reperfusion injury through iNOS inhibition in hyperthyroid rats.
abstract: Ischemic postconditioning (IPost) is a strategy to provide protection against ischemia-reperfusion (IR) injury. The cardioprotective effects of IPost in cases of ischemic heart disease along with co-morbidities like hyperthyroidism remain unknown. The aim of this study was to investigate the effects of IPost on expression of eNOS, iNOS, Bax, and Bcl-2 genes in hyperthyroid male rats, subjected to myocardial IR. Hyperthyroidism was induced by adding thyroxine to drinking water for a period of 21 days. Using the Langendorff device hearts were perfused, then subjected to a 30-minute global ischemia which was followed by 120 min of reperfusion; subsequently IPost was induced immediately after ischemia. Results indicated that following IR, expression of eNOS and Bcl-2 decreased, whereas expression of iNOS and Bax increased in both the control and hyperthyroid groups. In hyperthyroid animals, IPost significantly increased expression of eNOS by 3.19 fold and Bcl-2 by 3.66 fold; it also decreased expression of Bax by 51%, and reduced IR-induced DNA laddering pattern and infarct size (45.7 ± 1.82% vs. 59.3 ± 1.83%, p<0.05) in the presence of aminoguanidine (AG), a selective iNOS inhibitor. In conclusion, IPost per se could not provide cardioprotection against myocardial ischemia in hyperthyroid rats, a loss of which however was restored by the combination of IPost and iNOS inhibition that acts by a decrease in Bax and an increase in both eNOS and Bcl-2 expression.
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Jalal
authors.initials: J
authors.lastname: Zaman
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sajad
authors.initials: S
authors.lastname: Jeddi
authors.affiliation: Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam Sadat
authors.initials: MS
authors.lastname: Daneshpour
authors.affiliation: Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zarkesh
authors.affiliation: Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Daneshian
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
authors.forename: Asghar
authors.initials: A
authors.lastname: Ghasemi
mesh_terms: D000818:Animals; D017209:Apoptosis; D006980:Hyperthyroidism / Q000201:enzymology* / Q000473:pathology; D057775:Ischemic Postconditioning; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D052247:Nitric Oxide Synthase Type II
keywords: Gene expression; Hyperthyroidism; Ischemia; Postconditioning