In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts.

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 the left atrium and the left ventricle (3.62 ± 0.30, 2.96 ± 0.52, 1.64 ± 0.15, and 1.67 ± 0.22 nmoles/min g~\ respectively). Enzyme activity was reduced (P < 0.05) in the right atria and the right ventricles of guinea pigs with constriction of the pulmonary artery (1.68 ± 0.37 and 1.31 ± 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 hypertrophied 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. KEY WORDSparasympathetic neurotransmitter cardiac chambers carnitine acetyltransferase cardiac hypertrophy parasympathetic innervation of the heart choline acetyltransferase• In hypertrophied and failing hearts, defects in neurogenic control involve both sympathetic and parasympathetic abnormalities. These sympathetic defects are characterized by decreases in catecholamine biosynthesis and depletion of the sympathetic neurotransmitter (1-4), but the nature of the parasympathetic defects is uncertain (5). Depletion of the parasympathetic neurotransmitter, acetylcholine, has been postulated but not confirmed (6). Technical difficulties in the bioassay of acetylcholine emphasize the need for alternative assessments of cardiac parasympathetic innervation (7). Measuring the activity of choline acetyltransferase, the enzyme that catalyzes the This study was supported by U. S. Public Health Service Grants NS 11310, HL 02644, and HL 014388 from the National Institutes of Health and by a grant from the Veterans Administration.Received August 29, 1974. Accep...

Impaired cardiac muscarinic receptor function in dogs with heart failure.

“…However, in a model of total cardiac denervation, where sympathetic denervation is more complete than in this heart failure model, we detected only a 20% decrease in muscarinic receptor density (24). Furthermore, in terms of the parasympathetic system, Roskoski et al (25) have previously reported in an experimental model of heart failure in the guinea pig, that parasympathetic innervation as assessed by choline acetyl transferase levels, was reduced per unit weight, but not reduced in the entire ventricle. Their findings parallel our observations for muscarinic receptor density, which was reduced per milligram protein in the current investigation, but was not reduced in the entire ventricle, since hypertrophy had almost doubled the ventricular weight.…”

Differences in the regulation of vascular resistance in guinea pigs with right and left heart failure.

“…20 Also, the group with left heart failure produced by constriction of the ascending aorta, LHF A , was analogous to the experimental guinea pig models reported by Gertler, 21 Schwartz and Lee, 22 and Spann and co-workers. 23 The weights of the left ventricles plus septum and the weights of right ventricles were almost identical to those reported for a guinea pig model of left heart failure by Spann et al 23 In agreement with Spann and co-workers, 23 our preparations with left heart failure also exhibited modest right ventricular enlargement.…”

Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

“…There is extensive evidence confirming parasympathetic innervation of the mammalian ventricle as demonstrated by choline acetyltransferase activity, the presence of ACh, and muscarinic cholinergic receptors (55)(56)(57)(58)(59). However, there are conflicting data regarding the importance of direct vagal effects in the ventricular myocardium and the HPS.…”