The neural control of cardiac function involves interactions between the sympathetic and parasympathetic systems. These interactions are responsible for regulating various mechanisms within the heart.

Fig. 18.12 shows the interneuronal and intracellular mechanisms involved in these interactions. It includes various components such as adenylate cyclase (AC), acetylcholine (ACh), adenosine triphosphate (ATP), β-adrenergic receptor (β), beta/gamma (βγ), cyclic adenosine monophosphate (cAMP), stimulatory and inhibitory G proteins (Gs and Gi), muscarinic receptor (M), norepinephrine (NE), and neuropeptide Y (NPY).

Fig. 18.20 presents the effects of different concentrations of isoproterenol (Iso) on aequorin light signal and contractile force in a rat ventricular muscle injected with aequorin. The aequorin light signal indicates the changes in intracellular calcium levels. The results demonstrate the impact of isoproterenol on ventricular function.

Increased sympathetic nervous activity leads to an improvement in ventricular performance, allowing the ventricle to perform more work. On the other hand, the vagus nerves inhibit the cardiac pacemaker, atrial myocardium, and AV conduction tissue. Although the ventricular myocardium is also affected, the effects are less pronounced compared to the atria.

During vagal stimulation, the ventricular function curve shifts to the right, indicating reduced contractility. Vagus nerve stimulation suppresses the contractile force in the left ventricle, as shown in pressure-volume curves obtained at a constant ventricular rate (Fig. 18.21). The negative inotropic effect of vagus nerve stimulation, depicted as the reduced slope of the end-systolic pressure-volume relation, can be countered by a muscarinic receptor antagonist and diminished by a β-adrenoceptor antagonist. Therefore, vagus nerve stimulation decreases contractility through at least two pathways.

The mechanisms underlying the effects of vagal activity on the ventricular myocardium are illustrated in Fig. 18.19. Acetylcholine (ACh) released by the vagal nerves interacts with muscarinic receptors on the cardiac ventricular cell membrane. This interaction inhibits adenylate cyclase and the cAMP/protein kinase A cascade. As a result, the Ca++ conductance of the cell membrane diminishes, phosphorylation of the calcium channel decreases, and myocardial contractility is reduced. Additionally, ACh released from vagal nerves can inhibit norepinephrine release by activating muscarinic receptors on neighboring sympathetic nerves, which represents an indirect inhibition mechanism. Therefore, vagal activity can decrease ventricular contractility by counteracting any stimulatory effects exerted by concomitant sympathetic activity. Similarly, sympathetic nerves release norepinephrine and neuropeptide Y, which inhibits the release of ACh from neighboring vagal fibers (see Fig. 18.19).
Fig. 18.12 ). Hence, for any given left •Fig. 18.19 Interneuronal and Intracellular Mechanisms Responsible for Interactions Between the Sympathetic and Parasympathetic Systems in the Neural Control of Cardiac Function. AC,adenylatecyclase;ACh,acetycholine;ATP,adenosinetriphosphate;β,β-adrenergicreceptor;βγ,beta/gamma;cAMP,cyclicadenosinemonophosphate;GsandGi,stimulatoryandinhibitoryGproteins;M,muscarinicreceptor;NE,norepinephrine;NPY,neuropeptideY.(ModifiedfromLevyMN.In:KulbertusHE,FranckG,eds.Neurocardiology. Mt.Kisco,NY:Futura;1988.) •Fig. 18.20 Effects of Various Concentrations of Isoproterenol (Iso) on the Aequorin Light Signal (in Nanoamperes) and Contractile Force (in Millinewtons Per Square Millimeter) in a Rat Ventricular Muscle Injected With Aequorin. Theaequorinlightsignalreflectstheinstantaneouschangesinintracel-lular[Ca++].µM,micromolar.(ModifiedfromKuriharaS,KonishiM.Pflügers Arch. 1987;409:427.)0.1 sec Force Aequorin light signal 20 nA 0.2 µM Iso.0.1 µM Iso.0.05 µM Iso.Control 5 mN mm2 A B C D ventricular end-diastolic pressure, the ventricle can perform more work as sympathetic nervous activity is increased.
The vagus nerves inhibit the cardiac pacemaker, atrial myocardium, and AV conduction tissue. The vagus nerves also depress the ventricular myocardium, but the effects are less pronounced than in the atria. In pumping heart preparations, the ventricular function curve shifts to the right during vagal stimulation, an indication of reduced contractility. Vagus nerve stimulation suppresses the contractile force in the left ventricle. This is shown in pressure-volume curves obtained at constant ventricular rate (
Fig. 18.21 ). The negative inotropic effect of vagus nerve stimulation, depicted as the reduced slope of the end-systolic pressure-volume relation, is opposed by a muscarinic receptor antagonist and diminished by a β-adrenoceptor antagonist. The results indicate that vagus nerve stimulation reduces contractility in the heart and does so by at least two pathways.
Mechanisms for the vagal effects on the ventricular myocardium are shown in
Fig. 18.19 . ACh released by the vagal nerves interact with muscarinic receptors on the cardiac ventricular cell membrane to inhibit adenylate cyclase and the cAMP/protein kinase A cascade. This direct inhibition diminishes the Ca++ conductance of the cell membrane, reduces phosphorylation of the calcium channel, and hence decreases myocardial contractility. The ACh released from vagal nerves can also inhibit norepinephrine release by activating muscarinic receptors on neighboring sympathetic nerves, a mechanism of indirect inhibition. Thus vagal activity can decrease ventricular contractility partly by antagonizing any stimulatory effects that concomitant sympathetic activity may be exerting on ventricular contractility. Similarly, sympathetic nerves release norepinephrine and certain neuropeptides, including neuropeptide Y, which inhibits the release of ACh from neighboring vagal fibers (see
Fig. 18.19