The neuromodulation aspects of ischaemic myocardium: the importance of cholinergic system

Abstract

The ability of the heart to increase contractility and heart rate is facilitated by postganglionic sympathetic nerve endings that terminate within myocardium. In fact, the heart is often regarded as an "adrenergic" organ because beta-adrenergic agonists are powerful stimulants of cardiac contractility. Muscarinic cholinergic receptors mediate parasympathetic control of heart function. A primary effects of the muscarinic stimulation are opposite to those of beta-adrenergic stimulation. The modulation of an adrenergic receptors stimulation in the heart by cholinergic agonists may be the major means by which the muscarinic agonists alter heart function. When the hypoxic myocytes were exposed to adrenaline, the responsiveness of the cardiac cells to muscarinic stimuli had significantly increased, and a simultaneous potent increase in the expression of muscarinic receptors was observed. These result support the hypothesis that in ischaemic/hypoxic myocardium the role of cholinergic system may be more important than previously assumed. In this review an attempt was made to summarize the physiological and biochemical interactions in an autonomic nervous system in an ischaemic myocardium. The evidences of a relationship between ischaemia and inflammation are discussed. The better knowledge of feasible interactions of neuromodulators of an autonomic nervous system with myocardial and inflammatory cells, should lead to the development of successful pharmacological strategies for the prevention of ischaemic injury.