Chronic exercise induces pathological left ventricular hypertrophy in adrenaline-deficient mice

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Exercise Science

Background:

• Adrenaline deficiency in phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice leads to concentric cardiac remodeling.
• While resting blood pressure is normal, Pnmt-KO mice experience elevated blood pressure during acute exercise.

Purpose of the Study:

• To investigate cardiac morphological, functional, and molecular changes in adrenaline-deficient mice following chronic exercise.
• To assess the impact of chronic exercise on blood pressure, cardiac structure, and adrenergic responsiveness in Pnmt-KO mice.

Main Methods:

• Chronic exercise training (6 weeks) was performed on Pnmt-KO and wild-type (WT) mice.
• Cardiac morphology and function were assessed using echocardiography and hemodynamics.
• Left ventricle (LV) gene expression of IGF-1, IGF-1R, ANP, and BNP was quantified via real-time PCR.

Main Results:

• Trained Pnmt-KO mice displayed increased systolic blood pressure compared to trained WT mice.
• Significant increases in LV mass and LV posterior wall thickness were observed in trained Pnmt-KO mice versus trained WT mice.
• While WT mice showed improved systolic function with dobutamine, Pnmt-KO mice did not, indicating impaired β1-adrenergic response.

Conclusions:

• Adrenaline deficiency in Pnmt-KO mice results in concentric LV hypertrophy and a blunted response to dobutamine after chronic exercise.
• These findings suggest an early stage of pathological cardiac hypertrophic remodeling in Pnmt-KO mice.
• Efficient noradrenaline to adrenaline conversion is crucial for preventing blood pressure surges and pathological cardiac remodeling during chronic exercise.