PERIPHERAL AUTONOMIC MECHANISMS 



993 



sponses as before severance of the nerves. Consider- 

 able differences in the state of activity are found in 

 different effectors deprived of their autonomic nerves, 

 however. The cells of the adrenal iiiedijlla and of the 

 salivary and sweat glands show littl e if any activity. 

 This also holds for some smooth muscle, such as the 

 pilomotor, the orbital and the intraocular muscles. 

 The activitj^of most smooth muscle, on the other 

 hand, is more or less uninfluenced by denervation and 

 exhibits various types of rhythmic contractions, spon- 

 taneous in the sense that they are independent of 

 nervous impulses mediated through autonomic 

 ganglia. Several investigators have believed this spon- 

 taneous activity (e.g., 6, 148) to be dependent on a 

 terminal nervous network which does not degenerate 

 after postganglionic nerve section. As will be shown in 

 a later section, there is no valid evidence for the exist- 

 ence of such a structure but much good evidence 

 pointing in the other direction. Studies of the propa- 

 gated contractions and of the origin and conduction 

 of action potentials in sinooth muscle from the uterus, 

 ureter, intestine and stomach, especially by Bozler 

 (38-41, 217), have laid a good foundation for the 

 view that the spontaneous rhythmic contractions are 

 of myogenic origin and that conduction proceeds from 

 muscle cell to muscle cell and not through a nervous 

 network. This view has received strong support from 

 recent work by Biilbring (59, 60), Evans & Schild 

 (138), and by Prosser and his associates (347). 

 Whether conduction takes place in a syncytium of 

 muscle cells (Bozler, Biilbring) or perhaps by a sort of 

 ephaptic system between muscle fibers (Prosser) has 

 not yet been settled. Electronmicroscopic studies of 

 sinooth muscle from rat ureter have, however, demon- 

 strated a lack of protoplasmic continuity between the 

 cells and have revealed intercellular bridges assumed 

 to be ephaptic structures (19). 



That the smooth muscle of small blood vessels 

 regains its tone to a varying degree after denervation is 

 well-known and has usually been explained on the 

 basis of supersensitivity (cf 15). Strong arguments 

 against this theory have been presented by Cannon 

 (73) in experiments indicating that the recovered tone 

 might be due to intrinsic properties of the muscle 

 cells. There is now good evidence for the view that 

 the smooth muscle of blood vessels has a myogenic 

 automaticity like that found in, for instance, ureteral 

 muscle (cf. 82, 152). 



Supersensitivity of Autonomic Effector Cells 



It has long been known that various types of auto- 

 nomic effector cells deprived of their pre- or post- 



ganglionic nerve supply undergo changes leading to a 

 state of incjreased_sensitivity to epjnejjhrine, norepi- 

 nephrine, acetylcholine and other agents. As the in- 

 vestigations into this phenomenon have recentlv been 

 extensively reviewed by Cannon & Rosenblueth (77), 

 only a brief survey will be given. 



The supersensitivity of various smooth muscles 

 shows some common features such as increased sus- 

 ceptibility and increased duration of response to a 

 gi\-en agent, but the maximal response does not be- 

 come larger than in the muscles prior to denervation. 

 This also holds for glands (128, 399). The increased 

 sensitivity may develop quite rapidly, in some in- 

 stances within hours, as reported for the denervated 

 pupillary sphincter in the cat (388), or may become 

 maximal within two to four days as reported for the 

 sweat glands (391) and for the pupilloconstrictor 

 (237). In adrenergic systems the development of 

 supersensitivity generally takes a more prolonged 

 course, maximal sensitization being found after ^ Jo 

 3 weeks. The new state of excitability seems to remain 

 permanently, at least in most instances, but disappears 

 when regenerating nerve fibers become functionally 

 connected to the effector cells (389). 



Stipersensitivity has been shown to develop in the 

 most different cholinergic and adrenergic systems 

 supplied by both excitatory and inhibitory fibers. 

 Decentralized nerve cells in autonomic ganglia are 

 no exception (129, 364, 390). As might be expected, 

 a decentralized effector is supersensitive not only to 

 agents introduced from outside but also to the trans- 

 mitter liberated by stimulation of the postganglionic 

 nerve fibers (363). Finally, another general principle 

 is that denervated systems develop a higher degree of 

 supersensitivity than decentralized ones. 



The general principles for the development of 

 supersensitivity were formulated in 1939 by Cannon 

 into a 'law of denervation' : when in a series of effer- 

 ent neurons a unit is destroyed, an increased irritabil- 

 ity to chemical agents develops in the isolated struc- 

 ture or structures, the effects being maximal in the 

 part directly denervated. This has been confirmed on 

 the whole by the sub.sequent work in this field. Some 

 exceptions have been reported, however. Denervated 

 sweat glands in man, for instance, have been claimed 

 to be deserisitized (229) or to be unresponsive after 

 some time (216). The sensitivity of sweat glands in 

 the cat has been found to decrease a long time after 

 denervation (391). Conflicting results have been ob- 

 tained as regards the denervated heart (176, 220, 

 295). The evidence does not seem to be conclusive. 



There is as yet no generally accepted explanation 



