Summary
In order to better understand changes in markers of autonomic innervation associated with cardiac hypertrophy and failure, we measured myocardial acetylcholine (ACh) and norepinephrine (NE) after the injection of monocrotaline (MCT) in rats. We aslo determined 1,2-diacylgcerol (DAG), which is a second messenger activated by these neurotransmitters. At 2 weeks after MCT injection, right ventricular hypertrophy with no sign of heart failure occurred. Acetylcholine and 1,2-DAG concentrations increased by 29% and 55%, respectively, in the right ventricles. Four weeks later, decompensated heart failure was observed. In contrast to the 2-week hearts, the 4-week MCT right ventricles had a significant decrease in NE (-86%), ACh (-76%), and 1,2-DAG (-25%) concentrations, whereas there was no marked change in the left ventricles. These results indicate that parasympathetic innervation shows a transient increase during progressive hypertrophy due to pressure overload, accompanied by an increase in 1,2-DAG, and that NE, ACh, and 1,2-DAG are all depleted with the progression of overt heart failure.
Changes in cardiac autonomie innervation occur following the imposition of increased load on the heart. It is well known that the myocardial catecholamine store is depleted in congestive heart failure both in humans [1] and experimental animals [2,3]. Acute cardiac hypertrophy without failure induced by constriction of aorta or pulmonary artery results in reduction of the catecholamine store [4,5]. However, slowly progressive cardiac hypertrophy is not associated with the depression of sympathetic indices but with an increase in the norepinephrine store [6,7]. Both the spontaneously hypertensive rat [8] and the cardiomyopathic Syrian hamster during the compensated stage of heart failure [9] show an increase in myocardial catecholamine. Thus, the changes in sympathetic cardiac innervation vary, depending upon the stage and the time course of heart failure.
The parasympathetic nervous system also regulates ventricular function [10], and it does so not only directly but also by an indirect effect, which is mediated via parasympathetic modulation of the sympathetic effects. This sympathetic-parasympathetic interaction has been reported at both the inter- neuronal [11,12] and the intracellular [13] levels. When the activity of the sympathetic nervous system is increased, the effect of the parasympathetic nervous system becomes prominent [14].
It is well accepted that 1,2-diacylglycerol (DAG) is one of the second messengers in the transmembraneous cellular signal transduction system. An increase in 1,2-DAG followed by activating protein kinase C is the initial event in phosphoinositide hydrolysis, which is caused by the neurotransmitters norepinephrine (NE) [15] and acetylcholine (ACh) [16], a signaltransduction mechanism [17].
A single injection of monocrotaline (MCT) induces severe pulmonary hypertension and right ventricular pressure overload in rats with consequent development of right ventricular hypertrophy [18]. Monocrotaline-induced pulmonary hypertension is a convenient model for the study of both hypertrophy and cardiac failure. In this model, there appears to be an intrinsic control in the unaffected left side of the heart. This gives an advantage over models based on lesions affecting the left ventricle, which, secondarily, also affect the right side of the heart. It would be of great interest to investigate the serial changes in myocardial NE, ACh, and 1,2-DAG during the development of right ventricular hypertrophy and failure.
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Okumura, K. et al. (1995). Altered Myocardial Neurotransmitter and 1,2-Diacylglycerol Concentrations in Right Ventricular Hypertrophy and Failure in Rats. In: Singal, P.K., Dixon, I.M.C., Beamish, R.E., Dhalla, N.S. (eds) Mechanisms of Heart Failure. Developments in Cardiovascular Medicine, vol 167. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2003-0_5
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