Acetylcholine levels, choline acetyltransferase and acetylcholinesterase molecular forms during thyroxine-induced...

The effects of left ventricular hypertrophy induced by hyperthyroidism on three biochemical markers of parasympathetic innervation were investigated. In response to subcutaneous injections of thyroxine (400 micrograms/kg; T4) for 6 days, the left ventricle, but not the right, developed significant hypertrophy (20%). In the enlarged left ventricle, acetylcholine (ACh) content and choline acetyltransferase (ChAT) activity per chamber were elevated approx. 25-30%, although no change in these two markers was evident when the data were expressed per unit wet weight. Immunoblot analysis showed that the relative abundance of ChAT protein increased in the hypertrophied left ventricle in correlation with the increased ChAT activity. No changes in ACh content, ChAT activity and ChAT relative abundance were evident in the right ventricle of T4-treated animals. Although hyperthyroidism did not alter AChE specific activity (per unit wet weight) in the left ventricle, the percent activities of the individual AChE globular forms were affected in this chamber. Specifically, T4-treatment reduced the percent activity of globular (G)4 AChE by 20% and increased that of the combined G1 and G2 AChE pool by 15%. Interestingly, in the hypertrophied left ventricle total AChE activity in its extracellular or functionally-relevant pool was reduced due to a loss of G4 AChE activity. These results show that a compensatory increase in parasympathetic innervation can occur during hyperthyroid-induced left ventricular hypertrophy. However, the reduced activity of the functionally-relevant AChE pool suggests that the clearance of ACh after release may be slowed in the hypertrophied left ventricle.