title: Involvement of inducible nitric oxide synthase in the loss of cardioprotection by ischemic postconditioning in hypothyroid rats.
abstract: Cardioprotection by ischemic postconditioning (IPost) is negated in hypothyroidism; the underlying mechanisms however are unknown. This study aimed at determining whether changes in Bax, Bcl-2, eNOS, and iNOS gene expressions are involved in the negating effects of IPost against ischemia-reperfusion (IR) injury in hypothyroidism. The hearts from control and hypothyroid rats were perfused in Langendorff apparatus and exposed to 30 min ischemia, followed by 120 min reperfusion and IPost. In a subgroup of hypothyroid rats, ischemia duration was extended to 40 min. Hemodynamic parameters, infarct size, and gene expressions were measured. Compared to controls, hypothyroid rats with 30 min ischemia had higher recovery of post-ischemic LVDP and ± dp/dt, confirmed by decreased CK and LDH levels (187 ± 16 vs. 485 ± 41 and 191 ± 9 vs. 702 ± 48 U/L, respectively; p<0.05), decreased infarct size (6.7 ± 1.1 vs. 46.1 ± 1.7%; p<0.05), and a reduced DNA laddering pattern. Recovery of post-ischemic LVDP and ± dp/dt decreased and infarct size increased following extension of ischemia period in hypothyroid rats. IPost increased eNOS and Bcl-2 expression by 3.2-fold and 3.7-fold and decreased Bax and iNOS expression by 79% and 38%, respectively; it also reduced IR-induced DNA laddering pattern in controls, whereas no change was observed in hypothyroid rats, regardless of the ischemia period. In conclusion, hearts from hypothyroid rats were resistant to IR injury, partly due to the lower expression of iNOS and subsequent reduction in apoptosis after IR. In hypothyroid rats, IPost was not associated with further reduction in iNOS expression and failed to provide additional cardioprotection against ischemia.
authors.affiliation: Endocrine Physiology Research Center and 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: Endocrine Physiology Research Center and 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: Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azita
authors.initials: A
authors.lastname: Zadeh-Vakili
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: Endocrine Physiology Research Center and 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; D019610:Cytoprotection / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000235:genetics; D007037:Hypothyroidism / Q000503:physiopathology*; D057775:Ischemic Postconditioning; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Gene expression; Hypothyroid; Ischemia–reperfusion; Ischemic postconditioning; Nitric oxide