Nitric oxide synthase inhibition abolishes exercise-mediated protection against isoproterenol-induced cardiac hypertrophy in female mice.

Abstract

OBJECTIVE:

Exercise training (ET) provides a cardioprotective effect against pathological cardiac hypertrophy. Nitric oxide (NO) plays an important role in modulating cardiac hypertrophy. However, few studies explore the relationship between NO signaling and the inhibitory effect of ET on pathological cardiac remodeling.

METHODS:

In this study, we evaluated ET effects on isoproterenol (ISO)-induced cardiac hypertrophy in female mice. Moreover, L-NAME (Nω-nitro-L-arginine methyl ester), a nonselective NO synthase (NOS) inhibitor, was used to assess the involvement of NO signaling in cardiac hypertrophy. Morphological and echocardiographic variables were assessed. Cardiac hypertrophy-related gene expression was detected by real-time PCR and the protein levels of NOS signaling molecules were determined by Western blot.

RESULTS:

L-NAME treatment prevented the beneficial effects of ET against the increase in heart weight (HW)/body weight (BW), HW/tibia length and lung weight/BW and echocardiographic variables following ISO injection. Also, L-NAME co-administration reversed ET-induced inhibition of myocardial fibrosis and fetal gene reactivation in ISO-treated mice. Furthermore, L-NAME treatment prevented ET-mediated up-regulation of phosphorylated endothelial NOS and plasma NO in ISO-treated mice.

CONCLUSIONS:

Our findings demonstrate that L-NAME treatment could abolish ET-induced cardioprotection against pathological cardiac hypertrophy and that NOS modulation may be involved in the antihypertrophic effects induced by ET.

• Authors: Jiling Ren, Lei Yang, Wencong Tian, Mengmeng Zhu, Jie Liu, Ping Lu, Jing Li, Liang Yang, Zhi Qi
• Journal: Cardiology (Cardiology) Vol. 130 Issue 3 Pg. 175-184 ( 2015) ISSN: 1421-9751 [Electronic] Switzerland
• PMID: 25720823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel

Chemical References

• Enzyme Inhibitors
• Nitric Oxide
• Nitric Oxide Synthase
• Isoproterenol
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Blood Pressure (drug effects)
• Cardiomegaly (chemically induced, drug therapy, genetics)
• Disease Models, Animal
• Echocardiography
• Enzyme Inhibitors (therapeutic use)
• Female
• Fibrosis
• Isoproterenol (adverse effects)
• Mice
• Myocardium (pathology)
• NG-Nitroarginine Methyl Ester (therapeutic use)
• Nitric Oxide (blood)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Phosphorylation
• Physical Conditioning, Animal
• Real-Time Polymerase Chain Reaction
• Up-Regulation