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Published on: February 25, 2016
Nitric oxide synthase expressions in ADR-induced cardiomyopathy in rats
Baogang Liu1, Hongli Li, Hongyan Qu
1First Department of medicine, the Tumour Hospital of Harbin Medical University, Harbin, 150081, PR China.
Abstract:
In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADRtreated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.
Insights
Adriamycin (ADR) induces cardiomyopathy in rats, significantly increasing inducible nitric oxide synthase (iNOS) gene and protein expression in the heart. Neuronal NOS and endothelial NOS levels remained unchanged.
Area of Science:
- Cardiology
- Molecular Biology
- Toxicology
Background:
- Adriamycin (ADR) is an anthracycline chemotherapy agent with known cardiotoxic effects.
- Cardiomyopathy is a significant concern associated with ADR treatment.
- Nitric oxide synthase (NOS) plays a role in cardiovascular function and disease.
Purpose of the Study:
- To investigate the expression of three Nitric oxide synthase (NOS) isoforms in an Adriamycin (ADR)-induced cardiomyopathy rat model.
- To determine the specific NOS isoform(s) affected by ADR treatment in the myocardium.
- To explore the correlation between NOS expression and ADR-induced cardiac morphological changes.
Main Methods:
- Sixty male Wistar rats were divided into control and ADR-treated groups.
- Myocardial histopathology was assessed.
- Gene expression of three NOS isoforms (iNOS, nNOS, eNOS) was analyzed using RT-PCR.
- Protein expression of the three NOS isoforms was evaluated by Western blot analysis.
Main Results:
- ADR treatment led to significant myocardial morphological changes after 8 weeks.
- A significant increase in both inducible nitric oxide synthase (iNOS) gene and protein expression was observed in ADR-treated rats.
- No significant differences in neuronal NOS (nNOS) or endothelial NOS (eNOS) gene or protein expression were detected between groups.
- iNOS gene expression was selectively induced by ADR in the heart.
Conclusions:
- Adriamycin selectively induces iNOS expression in the rat heart.
- The upregulation of iNOS, both at the gene and protein level, may be linked to the observed morphological alterations in ADR-induced cardiomyopathy.
- nNOS and eNOS expression are not significantly affected by ADR-induced cardiotoxicity in this model.
