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In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts
Insights
Choline acetyltransferase activity, crucial for acetylcholine synthesis, was measured in guinea pig hearts under various constrictions. Despite cardiac changes, parasympathetic neurotransmitter biosynthesis remained largely unaltered in hypertrophied ventricles.
Area of Science:
- Cardiovascular Physiology
- Neurochemistry
- Cardiac Surgery
Background:
- Acetylcholine biosynthesis is regulated by choline acetyltransferase (ChAT) activity.
- Cardiac hypertrophy and heart failure can alter neurotransmitter systems.
- Parasympathetic innervation of the ventricles is less understood than atrial innervation.
Purpose of the Study:
- To investigate ChAT activity in all four heart chambers of guinea pigs with experimentally induced cardiac hypertrophy and failure.
- To compare ChAT activity changes with those of sympathetic neurotransmitter biosynthesis enzymes.
- To assess the impact of pressure overload on parasympathetic neurotransmitter synthesis in the heart.
Main Methods:
- Guinea pigs underwent sham surgery, ascending aorta constriction, descending thoracic aorta constriction, or pulmonary artery constriction.
- After 30 days, cardiac hypertrophy and failure were established.
- Choline acetyltransferase activity was quantified in vitro using a radiochemical assay in all four heart chambers.
Main Results:
- Sham-operated group showed highest ChAT activity in right atrium and ventricle.
- Pulmonary artery constriction significantly reduced ChAT activity in right atria and ventricles.
- Aortic constriction tended to reduce ChAT activity in left atria and ventricles, indicating relative dilution, not absolute depletion.
- Total ChAT activity per ventricle remained unchanged, contrasting with increased carnitine acetyltransferase.
Conclusions:
- Results confirm significant parasympathetic innervation in both atria and ventricles.
- No significant alterations in parasympathetic neurotransmitter biosynthesis were observed in hypertrophied and failing myocardium.
- This contrasts with previously reported reductions in sympathetic neurotransmitter biosynthesis enzymes like tyrosine hydroxylase.
Abstract:
Choline acetyltransferase activity, which is rate limiting in acetylcholine biosynthesis, was measured in the four heart chambers of guinea pigs subjected to (1) sham surgery, (2) constriction of the ascending aorta, (3) constriction of the descending thoracic aorta, and (4) constriction of the pulmonary artery. After 30 days when hypertrophy and heart failure were fully established, choline acetyltransferase was quantified in vitro by a radiochemical assay. In the sham-operated group, enzyme activity expressed in terms of unit weight of cardiac tissue was greatest in the right atrium and the right ventricle and lower in th left atrium and the left ventricle (3.62 plus or minus 0.30, 2.96 plus or minus 0.52, 1.64 plus or minus 0.15, and 1.67 plus or minus 0.22 nmoles/min g-1, respectively). Enzyme activity was reduced (P less than 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 plus or minus 0.37 and 1.31 plus or minus 0.29 nmoles/min g-1, respectively). Enzyme activity also tended to be reduced in the left atria and the left ventricles of guinea pigs with constriction of the aorta. These changes represented a relative dilution of enzyme activity per unit weight but not an absolute depletion, since choline acetyltransferase activity per ventricle was not reduced. The absence of significant changes in the total amount of the neuronal enzyme, choline acetyltransferase, per ventricle contrasted with the observed increases in the myocardial enzyme, carnitine acetyltransferase. These results confirm the presence of significant parasympathetic innervation of the ventricles as well as the atria but do not demonstrate alterations in parasympathetic neurotransmitter biosynthesis in hypertrphied and failing myocardium. The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis.