Neurochemical Heterogeneity in Sympathetic Ganglia and its Implications for Cardiovascular Regulation

Abstract

Sympathetic ganglia are important components of the neural circuitry for regulation of vascular tone and cardiac dynamics and may contribute to the pathophysiology of hypertension and heart failure. For a long time, these ganglia were viewed as simple relay stations where acetylcholine mediated the transfer of signals from the central nervous system to peripheral effector neurons. However, new information gathered over the past few decades has established that sympathetic ganglia are structurally and functionally more complex than previously envisioned. Numerous peptides have been identified in subpopulations of preganglionic nerve fibers that supply sympathetic ganglia. These peptides can be co-transmitters in cholinergic nerve fibers or transmitters in preganglionic nerve fibers that are non-cholinergic. Additionally, other classical transmitters besides acetylcholine have been identified in some preganglionic fibers. Several preganglionic fibers with different transmitters can surround individual postganglionic neurons. Postganglionic neurons can also receive input by collateral processes of sensory neurons, providing a mechanism for modulation of ganglion function by axon reflexes. Lastly, there is evidence that ganglionic transmission can be influenced through interneurons, presynaptic receptors on preganglionic nerve fibers, and by the actions of hormones and paracrine mediators. Collectively, these findings indicate that postganglionic neurons function as integrators. Most postganglionic sympathetic neurons are noradrenergic but these cells also express peptides (e.g., neuropeptide Y) as co-transmitters. Topographical distribution of chemically coded preganglionic fibers and target-dependent localization of postganglionic neurons have been identified in some sympathetic ganglia. As our understanding of the neurochemical, anatomical and functional complexities of sympathetic ganglia evolve, they may become attractive targets for the development of novel pharmaceuticals to treat cardiovascular diseases.