Related Experiment Video
Updated: Aug 20, 2026
Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice
Published on: October 3, 2019
Cardiac oxidative stress in acute and chronic isoproterenol-infused rats
Guo-Xing Zhang1, Shoji Kimura, Akira Nishiyama
1Department of Pharmacology, Kagawa University Medical School, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Objective:
Sympathetic nervous system activity in the myocardium is increased in patients with heart failure. However, the in vivo mechanisms responsible for beta-adrenoceptor-mediated cardiac hypertrophy or remodeling remain unclear. This study aimed to clarify the role of reactive oxygen species (ROS) in mitogen-activated protein (MAP) kinase activation and tissue remodeling of the heart of isoproterenol (ISO)-infused rats.
Methods And Results:
Different doses of ISO (up to 1000 ng/kg/min) were given intravenously to conscious rats for 30 min. Phosphorylated MAP kinase levels (ERK1/2, JNK, p38) and lipid peroxidation were measured in the cardiac left ventricle, revealing the dose-dependent augmentation of MAP kinase phosphorylation and increased lipid peroxidation levels. Simultaneous treatment with 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol), a membrane-permeable radical scavenger, completely eliminated the increases of phosphorylated MAP kinases and their upstream elements (Raf-1, Rac-1, ASK-1) as well as the increases of cardiac lipid peroxidation induced by the highest dose of ISO infusion. In chronically ISO-infused rats (3 mg/kg/day, s.c. for 10 days), cardiac hypertrophy developed with accompanying increases of collagen content, whereas cardiac phosphorylated MAP kinases returned to normal. Tempol treatment prevented increases of collagen accumulation and type I collagen mRNA without any significant reduction of cardiac mass enlargement induced by chronic ISO infusion.
Conclusion:
beta-Adrenoceptor stimulation provokes cardiac oxidative stress. In the acute phase of ISO infusion, ROS are important activators of cardiac MAP kinase cascades; while, in the chronic phase, ROS may participate in cardiac remodeling, especially in respect to wall stiffness, based on fibrogenesis.
Insights
Reactive oxygen species (ROS) activate cardiac mitogen-activated protein (MAP) kinases during acute beta-adrenoceptor stimulation. In chronic heart remodeling, ROS contribute to fibrogenesis and wall stiffness.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Oxidative Stress Research
Background:
- Increased sympathetic nervous system activity in heart failure.
- Unclear mechanisms of beta-adrenoceptor-mediated cardiac hypertrophy and remodeling.
Purpose of the Study:
- To clarify the role of reactive oxygen species (ROS) in mitogen-activated protein (MAP) kinase activation.
- To investigate ROS involvement in cardiac tissue remodeling during isoproterenol (ISO) infusion in rats.
Main Methods:
- Administered varying doses of ISO intravenously to conscious rats.
- Measured phosphorylated MAP kinase levels (ERK1/2, JNK, p38) and lipid peroxidation in cardiac left ventricle.
- Utilized Tempol, a radical scavenger, for simultaneous treatment in acute and chronic ISO infusion models.
Main Results:
- ISO infusion caused dose-dependent increases in MAP kinase phosphorylation and cardiac lipid peroxidation.
- Tempol treatment completely blocked acute MAP kinase activation and lipid peroxidation.
- Chronic ISO infusion led to cardiac hypertrophy and increased collagen, with Tempol preventing collagen accumulation but not mass enlargement.
Conclusions:
- Beta-adrenoceptor stimulation induces cardiac oxidative stress.
- ROS are key activators of cardiac MAP kinase cascades in the acute phase.
- ROS contribute to cardiac remodeling, particularly fibrogenesis and wall stiffness, in the chronic phase.
