chart. Discuss the Autonomic nervous system\'s (ANS) innervation of the cardiova
ID: 3481074 • Letter: C
Question
chart. Discuss the Autonomic nervous system's (ANS) innervation of the cardiovascular system. In other words, where does the parasympathetic innervate? The sympathetic? What are their effects at each of these places? How do they ultimately affect MAP? What is this reflex called that corrects for changes in MAP? What are the receptors of pressure? A category of drugs known as beta-blockers exert their actions by blocking the beta- adrenergic receptors for norepinephrine in the heart. What effect do you predict these drugs will have on heart function? (15 points) 1.Explanation / Answer
Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.
Cardiac autonomic nerves are closely spatially associated with cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodelling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory function, including in possible neurotransmitter changes. Certainly, neurotrophins and cytokines regulate transcriptional factors in adult autonomic neurons that have vital differentiation roles in development. Particularly for parasympathetic cardiac ganglion neurons, additional examinations of developmental regulatory mechanisms will potentially aid in understanding attenuated parasympathetic function in a number of conditions, including heart failure.
Sympathetic and parasympathetic branches of the cardiac autonomic nervous system (ANS) work in a reciprocal fashion to modulate heart rate (chronotropy) and conduction velocity (dromotropy) primarily through actions on cardiac pacemaker tissue. In addition, sympathetic nerves innervate atrial and ventricular cardiomyocytes and can thereby influence force of contraction (inotropy) and relaxation (lusitropy). Postganglionic cardiac sympathetic neurons have their cell bodies primarily in the paravertebral stellate (inferior-middle cervical) ganglion neurons; 92% of retrogradely-labelled nerves from the heart have their origins in this ganglion. These sympathetic neurons primarily utilize norepinephrine as their principal neurotransmitter, although other neuropeptides, such as neuropeptide Y (NPY) and galanin, are also co-released from sympathetic terminals. Among other functions, NPY and galanin decrease acetylcholine release from adjacent parasympathetic terminals. Parasympathetic neurons receive pre-ganglionic inputs from the vagus and have their cell bodies within the cardiac ganglia. The mammalian cardiac ganglia are arranged in discrete locations within the atrial epicardium closely associated with epicardial fat, in ganglionated plexi along the walls of the major cardiac vessels, and some are also present within the ventricular wall. The primary neurotransmitter in cardiac ganglion neurons is acetylcholine; however, like the sympathetic nerves, neuropeptides such as the vasoactive intestinal polypeptide (VIP) may also be co-released from parasympathetic terminals, as is nitric oxide. Parasympathetic attenuation of heart rate is effected primarily through hyperpolarization of nodal tissue, both sino-atrial and atrioventricular.
For heart rate control, the close physical proximity of postganglionic cardiac parasympathetic and sympathetic axons in pacemaker regions allows formation of axo-axonal synapses and reciprocal modulation of function, through either acetylcholine inhibition of norepinephrine release or vice versa. Despite mutual modulation, vagal influences on the sinus node predominate over sympathetic effects; however, vagally induced bradycardia is greater in the presence of tonic sympathetic stimulation. Hence, the concept of accentuated antagonism has emerged to define the functional relationship between these systems.
An additional layer of complexity within peripheral autonomic limb interactions lies in the intrinsic cardiac nervous system. In addition to a simple relay function for conveying preganglionic vagal impulses, integration of parasympathetic, sensory and sympathetic inputs via local circuit neurons occurs within cardiac ganglia. This level of integration has been studied in detail and is critical for allowing the formation of rapid temporal reflexes that can enable local regulation of heart rate on a beat-to-beat basis. Key to this integration, aside from intraganglionic crosstalk, are interganglionic connections and descending inputs. Axo-somatic connections between sympathetic nerves and parasympathetic neurons also mediate prejunctional autonomic interactions within the cardiac ganglia; for the right atria, these interactions involve neurons in the posterior atrial ganglionated plexus. In contrast, ablation of the right atrial ganglionated plexus attenuates vagal bradycardia while retaining vagal inhibition of sympathetic function. Indeed, Armour and colleagues have demonstrated that local circuit neurons, those that do not project their axons beyond the ganglion, constitute a majority of the neurons in the mammalian cardiac ganglion. Cardiac ganglia, therefore, represent an important site for investigations into peripheral autonomic interactions.
The development of cardiac autonomic innervation has four distinct phases; neural crest cell (NCC) migration to the dorsal aorta, differentiation of NCCs into neurons, aggregation/migration of neurons to form either the paravertebral sympathetic chains or the parasympathetic cardiac ganglia, and finally an extension of axonal projections into cardiac tissue and terminal differentiation. Throughout this period, extending into early postnatal life, autonomic neurons and their precursors display substantial plasticity. From a developmental perspective, as autonomic control matures, there can be serious consequences for the fetus/infant if blood pressure and heart rate are unduly perturbed. In normal infants, sympathetic cardiac control decreases with postnatal age and parasympathetic control over heart rate increases.40 Conversely, in preterm infants, since maturation is incomplete, blood pressure and heart rate control are impaired and may be causative in sudden infant death syndrome. Preterm/low birth weight infants also have an increased risk of developing hypertension, coronary heart disease and ischemic heart disease in adulthood. Although a link with cardiac autonomic control has not been established for this group of at-risk children, the ANS may be causative in a number of childhood cardiovascular disease states as it certainly is in adulthood. For example, it has already been demonstrated that increased cardiac sympathetic activation and parasympathetic depression occurs in low-income children and children with sickle cell anaemia. Certainly, adult rat offspring of either nutritionally-deprived mothers, or obese mothers, have elevated sympathetic tone that manifests in increased blood pressure and heart rate. Similarly, in genetically hypertensive rats, significant sympathetic acceleration of the heart is observed in the early postnatal period (P4) suggesting a possible mechanism for subsequent hypertension development. Altered autonomic maturity in infancy may, therefore, have long-lasting consequences, and this is an expanding field of study.
Although deficits in cardiovascular regulation can occur at all levels of neuronal control, there is increasing appreciation that aberrant nerve growth and plasticity in the effector cardiac nerves may have major roles in many cardiac disease processes. Intriguingly, many of the neuroplastic alterations observed in adult cardiac ANS neurons can be traced back to various stages in their development, so the importance of further delineating ontogenetic pathways for these neurons is of substantial importance for future translational studies. This is particularly true for parasympathetic cardiac ganglion neurons for which developmental mechanisms have not been worked out as well as for cardiac sympathetic neurons.
Special pressure sensors called baroreceptors (or venoatrial stretch receptors) located in the right atrium of the heart detect increases in the volume and pressure of blood returned to the heart. These receptors transmit information along the vagus nerve (10th cranial nerve) to the central nervous system.
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