Figure 8.1. summary of cell types mediating ureteral contraction.

Mucosa

Lumen

Inner layer of longitudinal muscle Outer layer of

circular muscle Loose connective

tissue Ureter cross section

Ureteropelvic junction

Ureter

Ureter crossing over iliac vessels

Common iliac vessels

Ureterovesical junction

1,4,5-triphosphate and diacylglycerol cause increased contraction, whereas mediation of G-protein coupled receptor complexes via cAMP and cGMP reduce contraction by lowering calcium levels.6

Urinary tract pacemaking originates in the pelvicalyceal junctions. This is known from experiments demonstrating aperistalsis of human preparations with only the renal pelvis and major calyx, and peristalsis when the specimen includes the minor calyx.7

It has become clear that peristalsis is initiated not by neurons, but rather by smooth muscle itself, as experiments using tetrodoxin or autonomic nerve blockers fail to block ureteral contractions.8 In addition, denervated transplant ureters are able to maintain contractility.9

Ureteral pacemaking involves three types of cells: typical, atypical, and renal interstitial cells.10 Signaling initiates within the atypical cells and ultimately passes to typical cells,but receives modulatory influence from the renal interstitial cells. Renal interstitial cells demonstrate c-kit receptor positivity.11 Such receptors can be influenced by outside influences such as the nervous system, prostaglandins, and other hormones, causing changes in contractility in different situations.12 Renal interstitial cells with c-kit positivity are more numerous in the upper ureter,explaining the higher rate of contractility in this area11 (Fig. 8.2).

Modulation of Peristalsis

While initiation of ureteral contraction is to some degree independent from the nervous

system, modulation of peristalsis relies heavily on the autonomic and sensory nervous system, as well as prostaglandins. Ureteral contraction can vary with regard to rate and contractility.

The autonomic nervous system influences ureteral contraction through both parasympathetic and sympathetic fibers. The parasympathic nervous system acts via muscarinic receptors with acetylcholine as its major neurotransmitter.Significant evidence indicates that the effect of such cholinergic stimulation varies by species. For example, in anesthetized dogs with obstructed ureters, parasympathic stimulation results a decrease in peristaltic rate and contractility.13 In a pig model, however, muscarinic stimulation causes an increase in rate and contractility, although only in the proximal ureter.14 In humans, it is generally believed that cholinergic stimulation results in an increase in the rate and force of ureteral contractions, although these effects are much more subtle than in the bladder.1 The sympathetic nervous system affects ureteral function in three ways:

1.Directly modulating ureteral contraction

2.Influencing pacemaking

3.Mediating ureteral contraction.

It has been shown that administration of norepinephrine in an obstructed ureter results in increased spasm and decreased flow at the area of obstruction.14 This can be reversed with the alphablocker phentolamine.15 Beta agonists, however, clearly cause ureteral relaxation. This effect has been demonstrated in pigs as well as humans.16

Sensory nerves are able to modulate peristalsis via capsaicin-sensitive fibers. The sensory