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Published on: February 25, 2016
Influence of the chronic nitric oxide synthesis inhibition on cardiomyocytes number
M G Pessanha1, C A Mandarim-de-Lacerda
1Laboratório de Morfometria, UERJ, Instituto de Biologia, Centro Biomédico, Rio de Janeiro, Brasil. mgpessanha@hotmail.com
Insights
Hypertension in rats led to a significant decrease in cardiomyocyte numerical density, not due to proliferation but apoptotic cell death. This programmed cell death appears to be mediated by a p53-dependent pathway.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Hypertension Research
Background:
- Hypertension is a major risk factor for cardiovascular disease, often leading to cardiac remodeling.
- Understanding the cellular mechanisms underlying hypertensive cardiomyopathy is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the relationship between cardiomyocyte number and growth response in a rat model of hypertension.
- To elucidate the cellular mechanisms, including proliferation and apoptosis, contributing to cardiomyocyte loss in hypertension.
Main Methods:
- Hypertension was induced in Wistar rats using NG-nitro-L-arginine methyl ester (L-NAME) for 15 weeks.
- Cardiomyocyte proliferation was assessed by Proliferating Cell Nuclear Antigen (PCNA) expression.
- Apoptosis was detected using Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and anti-single-stranded DNA antibody.
- p53 expression was analyzed to investigate its role in apoptosis.
Main Results:
- L-NAME induced hypertension resulted in a 60% decrease in cardiomyocyte numerical density (Nv[m]).
- No PCNA labeling was observed, indicating a lack of cardiomyocyte proliferation.
- Increased apoptotic cell death was detected in the myocardium of hypertensive rats.
- p53 expression was associated with the observed apoptosis.
Conclusions:
- Hypertension-induced reduction in cardiomyocyte number is primarily due to apoptotic cell death, not impaired proliferation.
- A p53-dependent pathway appears to mediate programmed cell death in this hypertensive rat model.
- These findings highlight apoptosis as a key mechanism in hypertensive cardiomyopathy progression.
Abstract:
This work analyzes the relationship between the number of viable cells and alteration of the cardiomyocytes growth response capacity of the hypertensive rat myocardium. Hypertension was induced in Wistar rats by means of nitric oxide synthesis blockade using NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (12 mg/kg per day) was given to animals in drinking water ad lib for 15 weeks. Proliferating cell nuclear antigen (PCNA) protein expression and the disector method were used to evaluate the proliferation capacity of the cardiomyocytes and its numerical density alteration (Nv[m]), respectively. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and monoclonal antibody to single-stranded DNA were two methods that detected the process of the apoptotic cell death. The association of the p53 expression with the apoptosis was investigated using anti-p53 antibody. The heart weight, body weight, and heart weight/body weight ratio of the control rats increased 114%, 77%, and 22%, respectively, and the Nv[m] decreased 60% (P<0.0001) relative to the L-NAME rats. The cardiomyocytes did not present PCNA labeling, indicating the absence of cellular proliferation. The decline of the Nv[m] was also associated with apoptotic cell death in the myocardium of the hypertensive rats. A p53-dependent pathway seems to mediate the programmed cell death in this model of hypertension.
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