Cardiac sympathetic rejuvenation: a link between nerve function and cardiac hypertrophy

Area of Science:

• Cardiovascular Physiology
• Neurobiology
• Molecular Biology

Background:

• Cardiac hypertrophy alters growth factor expression, impacting cardiac sympathetic nerves.
• Nerve growth factor's role in cardiac sympathetic nerve changes during hypertrophy is poorly understood.

Purpose of the Study:

• To investigate the effects of pressure overload-induced cardiac hypertrophy on cardiac sympathetic nerve innervation density and function.
• To analyze norepinephrine synthesis, reuptake kinetics, and neuronal gene expression in hypertrophic hearts.

Main Methods:

• Induced right ventricular hypertrophy in Wistar rats using monocrotaline.
• Assessed sympathetic nerve markers (beta(3)-tubulin, GAP43, tyrosine hydroxylase) and nerve growth factor.
• Measured norepinephrine and dopamine content, tyrosine hydroxylase activity, and neurotransmitter reuptake.

Main Results:

• Marked increase in new sympathetic nerves and nerve growth factor in the hypertrophic right ventricle.
• Paradoxical decrease in norepinephrine and dopamine content, with downregulated tyrosine hydroxylase.
• Diminished reuptake of key neurotransmitters, indicating functional nerve impairment.
• Expression of immature neuron marker (PSA-NCAM) in hypertrophic cardiac sympathetic nerves.

Conclusions:

• Pressure overload leads to anatomical sympathetic hyperinnervation but functional deterioration of cardiac nerves.
• This functional decline is associated with nerve 'rejuvenation' and fetal gene expression in cardiomyocytes.