Changes in nitric oxide synthase levels are associated with impaired cardiac function and tolerance to ischemia-reperfusion injury in male rats with transient congenital hypothyroidism
Transient congenital hypothyroidism (TCH) has long-lasting consequences on the cardiovascular system during adulthood. The aim of this study was to determine whether nitric oxide (NO) and NO-producing enzymes are involved in impaired cardiac function as well as decreased tolerance to ischemia-reperfusion (IR) injury in adult male rats with TCH. Pregnant rats were divided into control and hypothyroid groups. Male offspring rats were categorized in control and hypothyroid (TCH) groups at week 16. Levels of NOx (nitrate+nitrite) and neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS) were measured in hearts of rats and isolated perfused hearts from both groups were subjected to IR. Levels of NOx and NOSs were also measured in both groups after ischemia. Compared with controls, heart NOx levels were higher at baseline (48.0 ± 4.9 vs. 35.0 ± 2.6 μmol/L; P = 0.034) and following IR (103.6 ± 4.2 vs. 70.2 ± 2.7 μmol/L; P < 0.001) in rat with TCH. At baseline, compared with controls, heart iNOS and nNOS levels were significantly higher in rats with TCH (6.12 ± 0.34 vs. 4.78 ± 0.27 ng/mg protein; P = 0.008 for iNOS and 4.87 ± 0.28 vs. 3.55 ± 0.23 ng/mg protein; P = 0.003 for nNOS). Following IR, in rats with TCH, heart iNOS levels increased (11.75 ± 2.02 vs. 6.12 ± 0.34, ng/mg protein; P = 0.015) whereas nNOS level decreased (4.10 ± 0.25 vs. 4.87 ± 0.28 ng/mg protein; P = 0.063). Adverse effects of TCH on cardiac function are associated with increased ratio of iNOS/eNOS; in addition, increased heart nNOS levels are involved in impaired cardiac function while its decrease is associated with decreased tolerance to IR injury.
KeywordsTransient congenital hypothyroidism Nitric oxide Cardiac function Neuronal NOS Inducible NOS Endothelial NOS
The authors wish to acknowledge Ms.Niloofar Shiva for the critical editing of English grammar and syntax of the manuscript.
MGH and AGH conceived and designed the research. MGH, SJ, RN, and FB performed experiments and analyzed the data. MGH, SJ, and AGH wrote the manuscript. All authors have read and approved the manuscript.
This study was supported by a Grant No 915 by the Research Institute for Endocrine Sciences of RIES Shahid Beheshti University of Medical Sciences.
Compliance with ethical standards
All experimental procedures employed, as well as rat care and handling, were in accordance with guidelines provided by the local ethics committee of the RIES of Shahid Beheshti University of Medical Sciences. (Ethic code: IR.SBMU.Endocrine.Rec.1396.398).
Conflict of interest
The authors declare that they have no competing interests.
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