Sport Physiology

Sport Physiology

The Effect of Continuous and Interval Training with Different Intensities on PDE9A Gene Expression and Serum NO Levels in a Rat Model of Myocardial Infarction

Document Type : Research Paper

Authors
Gholamreza Sharifi 1
Shiva Sadeghi 2
Khosro jalali dehkordi 2
1 PhD student, Department of Sports Physiology, Faculty of Sports Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
2 Associate Professor, Department of Sports Physiology, Isfahan Branch (Khorasgan), Islamic Azad University, Isfahan, Iran.
10.22089/spj.2026.17837.2359
Abstract
Extended Abstract
Background and Purpose
Cardiovascular diseases (CVDs) are major causes of mortality and disability worldwide, with myocardial infarction (MI) being a leading complication. MI occurs due to coronary artery blockage, resulting in ischemic damage and loss of cardiac tissue. Phosphodiesterase 9A (PDE9A) has emerged as a key regulator of myocardial function through modulation of cyclic guanosine monophosphate (cGMP) signaling. Altered PDE9A expression is associated with impaired nitric oxide (NO) signaling, myocardial remodeling, and reduced cardiac performance after ischemic injury. Exercise training is a non-pharmacological approach known to improve cardiac health and regulate molecular pathways related to cardiac repair. Considering the interaction between PDE9A and NO signaling, exercise may influence their expression and activity. Therefore, this study aimed to evaluate the effects of eight weeks of continuous and interval exercise training on PDE9A gene expression and serum nitric oxide (NO) levels in an animal model of myocardial infarction.

Materials and Methods
This experimental laboratory study was conducted on forty adult male Wistar rats. After one week of environmental adaptation and treadmill familiarization (10 min/day at 6 m/min for five consecutive days), the animals were randomly assigned to five groups: healthy control, MI control, continuous training (70% of maximal running speed), and two interval training groups at 80% and 90% of maximal running speed.Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (150 mg/kg) on two consecutive days, with the dosage determined based on pilot experiments. Successful MI induction was confirmed through behavioral alterations, macroscopic discoloration of cardiac tissue, and comparison with established histopathological evidence. Following a 48-hour recovery period, the main training intervention commenced and continued for eight weeks, consisting of three sessions per week lasting 30 minutes each. Maximal running speed was determined via a progressive treadmill test, in which speed increased by 3 m/min every two minutes until exhaustion.Serum nitric oxide (NO) concentrations were measured using a commercial ELISA kit, while PDE9A gene expression was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using specific primers. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test to determine group differences. All data were analyzed using SPSS software version 19, and statistical significance was set at P ≤ 0.05. Graphical illustrations were generated using GraphPad Prism software.

Results
The present study examined the effects of continuous and interval exercise training on PDE9A gene expression and nitric oxide (NO) levels in the cardiac tissue of healthy and myocardial infarction (MI)-induced rats. One-way ANOVA revealed a significant difference in PDE9A expression among the experimental groups (F(4,35) = 14.2, p < 0.001). Tukey’s post hoc test showed that PDE9A expression was significantly higher in the MI control group compared to all other groups (p < 0.001). Exercise interventions led to a significant reduction in PDE9A expression compared with the MI group, with the greatest decrease observed in the moderate-intensity interval training group (interval training 1), where the expression levels were nearly comparable to those of the healthy control group (p ≤ 0.05). These results indicate that exercise, particularly interval training, can suppress the MI-induced overexpression of the PDE9A gene.Similarly, the analysis of nitric oxide (NO) levels demonstrated significant differences among the groups (F(4,35) = 18.5, p < 0.001). According to Tukey’s post hoc test, NO levels were markedly reduced in the MI control group compared to all other groups (p < 0.001). Both continuous and interval exercise training significantly increased NO concentrations relative to the MI group, with the highest levels observed in the moderate-intensity interval training group. This improvement suggests that interval exercise enhances NO bioavailability through the activation of the NO–cGMP–PKG signaling pathway. Consequently, such adaptations may contribute to improved endothelial function and reduced oxidative stress following myocardial injury, ultimately providing cardioprotective effects. Overall, these findings demonstrate that exercise training, especially moderate-intensity interval training, effectively downregulates PDE9A expression and enhances NO levels in cardiac tissue after MI, supporting its therapeutic potential in myocardial recovery and remodeling.

Conclusion
The results of this study demonstrate that eight weeks of continuous and interval exercise training at different intensities can effectively decrease PDE9A gene expression and increase serum nitric oxide (NO) levels. Among the exercise protocols, interval training at 80% of maximal running speed produced the most pronounced improvements in both parameters. These findings suggest that exercise, particularly appropriately prescribed interval training, may serve as an effective non-pharmacological intervention for protecting cardiac tissue following myocardial infarction. Moreover, the observed modulation of PDE9A and NO indicates that exercise training could complement pharmacological strategies aimed at improving cardiac recovery and remodeling after ischemic injury. Therefore, targeted exercise programs may represent a promising adjunctive approach in the prevention and rehabilitation of post-infarction cardiac dysfunction.

Article Message
Cardiovascular diseases remain a leading cause of mortality worldwide, with myocardial infarction often triggering adverse cardiac remodeling and heart failure. The findings of this study underscore the critical role of exercise training, particularly moderate-intensity interval training, in regulating cardiac molecular pathways post-infarction. By specifically reducing PDE9A gene expression—an enzyme that degrades cGMP and impairs nitric oxide (NO) signaling—exercise significantly enhances NO bioavailability. This mechanism contributes to the restoration of myocardial function and attenuates detrimental post-infarction cardiac remodeling. These results emphasize that properly designed exercise protocols serve as effective non-pharmacological strategies for cardiovascular protection and rehabilitation. Furthermore, the modulation of the PDE9A–NO signaling axis by exercise provides a promising foundation for combined therapeutic approaches. Integrating exercise with pharmacological interventions could optimize cardiac recovery after ischemic injury, offering new avenues to improve patient outcomes and reduce the burden of heart failure.

Ethical Considerations
The present study adhered to the ethical principles for working with laboratory animals in accordance with the guidelines of the International Committee and the Ethics Committee of Islamic Azad University, Isfahan (Khorasgan) Branch (IR.IAU.KHUISF.REC.1398.136).
Authors’ Contributions
All authors contributed in the design, execution, and writing of every section of this research.

Conflict of Interest
The authors declare that there are no conflicts of interest associated with this study.

Acknowledgments
We sincerely appreciate the support and contributions of all those who assisted us in this research endeavor.
 
Keywords
Myocardial Infarction
Phosphodiesterase
Interval Training
Continuous Training
Nitric Oxide

Subjects

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  • Receive Date 16 June 2025
  • Revise Date 26 February 2026
  • Accept Date 07 March 2026