Functional Organization of Autonomic Activity

Autonomic function is integrated and regulated at many levels, from the CNS to the effector cells. Most regulation uses negative feedback, but several other mechanisms have been identified. Negative feedback is particularly important in the responses of the ANS to the administration of autonomic drugs.

Central Integration:

At the highest level—midbrain and medulla—the two divisions of the ANS and the endocrine system are integrated with each other, with sensory input, and with information from higher CNS centers, including the cerebral cortex. These interactions are such that early investigators called the parasympathetic system a trophotropic one (ie, leading to growth) used to "rest and digest" and the sympathetic system an ergotropic one (ie, leading to energy expenditure), which is activated for "fight or flight." Although such terms offer little insight into the mechanisms involved, they do provide simple descriptions applicable to many of the actions of the systems. For example, slowing of the heart and stimulation of digestive activity are typical energy-conserving and storing actions of the parasympathetic system. In contrast, cardiac stimulation, increased blood sugar, and cutaneous vasoconstriction are responses produced by sympathetic discharge that are suited to fighting or surviving attack.

Direct Effects of Autonomic Nerve Activity on Some Organ Systems. Autonomic Drug Effects Are Similar But Not Identical.

Organ Effect of Sympathetic Activity Parasympathetic Activity Action1   Receptor2   Action Receptor2   Eye    Iris radial muscle Contracts 1   . . . . . .   Iris circular muscle . . . . . . Contracts M3     Ciliary muscle [Relaxes] Contracts M3   Heart    Sinoatrial node Accelerates 1, 2   Decelerates M2     Ectopic pacemakers Accelerates 1, 2   . . . . . .   Contractility Increases 1, 2   Decreases (atria) M2   Blood vessels    Skin, splanchnic vessels Contracts . . . . . .   Skeletal muscle vessels Relaxes 2   . . . . . . [Contracts] . . . . . . Relaxes3   M3   . . . . . .   Endothelium (drug effect) Releases EDRF4   M3, M55   Bronchiolar smooth muscle  Relaxes 2   Contracts M3   Gastrointestinal tract    Smooth muscle     Walls Relaxes 2,6 2   Contracts M3       Sphincters Contracts 1   Relaxes M3     Secretion . . . . . . Increases M3   Genitourinary smooth muscle    Bladder wall Relaxes 2   Contracts M3     Sphincter Contracts 1   Relaxes M3     Uterus, pregnant Relaxes 2   . . . . . . Contracts Contracts M3     Penis, seminal vesicles Ejaculation Erection M Skin    Pilomotor smooth muscle Contracts . . . . . .   Sweat glands . . . . . .     Eccrine Increases M . . . . . .     Apocrine (stress) Increases . . . . . . Metabolic functions    Liver Gluconeogenesis 2,   . . . . . .   Liver Glycogenolysis 2,   . . . . . .   Fat cells Lipolysis 3   . . . . . .   Kidney Renin release 1   . . . . . .

At a more subtle level of interactions in the brain stem, medulla, and spinal cord, there are important cooperative interactions between the parasympathetic and sympathetic systems. For some organs, sensory fibers associated with the parasympathetic system exert reflex control over motor outflow in the sympathetic system. Thus, the sensory carotid sinus baroreceptor fibers in the glossopharyngeal nerve have a major influence on sympathetic outflow from the vasomotor center. This example is described in greater detail in the following text. Similarly, parasympathetic sensory fibers in the wall of the urinary bladder significantly influence sympathetic inhibitory outflow to that organ. Within the ENS, sensory fibers from the wall of the gut synapse on both preganglionic and postganglionic motor cells that control intestinal smooth muscle and secretory cells.

Integration of Cardiovascular Function:

Autonomic reflexes are particularly important in understanding cardiovascular responses to autonomic drugs. The primary controlled variable in cardiovascular function is mean arterial pressure.  Changes in any variable contributing to mean arterial pressure (eg, a drug-induced increase in peripheral vascular resistance) evoke powerful homeostatic  secondary responses that tend to compensate for the directly evoked change. The homeostatic response may be sufficient to reduce the change in mean arterial pressure and to reverse the drug's effects on heart rate. A slow infusion of norepinephrine provides a useful example. This agent produces direct effects on both vascular and cardiac muscle. It is a powerful vasoconstrictor and, by increasing peripheral vascular resistance, increases mean arterial pressure. In the absence of reflex control—in a patient who has had a heart transplant, for example—the drug's effect on the heart is also stimulatory; that is, it increases heart rate and contractile force. However, in a subject with intact reflexes, the negative feedback response to increased mean arterial pressure causes decreased sympathetic outflow to the heart and a powerful increase in parasympathetic (vagus nerve) discharge at the cardiac pacemaker. This response is mediated by increased firing by the baroreceptor nerves of the carotid sinus and the aortic arch. Increased baroreceptor activity causes the changes mentioned in central sympathetic and vagal outflow. As a result, the net effect of ordinary pressor doses of norepinephrine in a normal subject is to produce a marked increase in peripheral vascular resistance, an increase in mean arterial pressure, and a consistent slowing of heart rate. Bradycardia, the reflex compensatory response elicited by this agent, is the exact opposite of the drug's direct action; yet it is completely predictable if the integration of cardiovascular function by the ANS is understood.

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