It is likely that the spontaneous contractile activity of the rat upper urinary tract arises from the discharge of action potentials in typical smooth muscle cells of the proximal renal pelvis that are directly driven by the spontaneous membrane oscillations of atypical smooth muscle cells.

The unique function of the upper urinary tract is to propel urine from the kidneys into the ureter and the bladder for storage until micturition. The mechanisms by which the ureter propels urine have long been considered to be myogenic in origin as peristaltic contractions in vivo propagate in a manner unaffected by the application of drugs that block the parasympathetic and sympathetic innervation or nerve conduction (

1 The role of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in the upper urinary tract of the guinea-pig and rat was examined using simultaneous tension recordings of the proximal and distal regions of the renal pelvis and the ureter. 2 The guinea-pig upper urinary tract contracted at a frequency (7.52+0.3 min 71 at 358C) signi®cantly lower than the frequency in the proximal renal pelvis (21.6+1.3 min 71) and in the distal renal pelvis and ureter (20.2+1.4 min 71 ) of the rat (at 308C). 3 Indomethacin (51 mM for 60 min), decreased the motility index (amplitude6frequency) (MI) in all three regions of the guinea-pig upper urinary tract, an eect which mainly arose from a decrease in the frequency of contractions. In the rat, indomethacin (1 ± 30 mM for 60 min) signi®cantly decreased the MI calculated in the proximal renal pelvis (530 mM indomethacin), and in the distal renal pelvis (510 mM indomethacin), arising from a signi®cant decrease in the amplitude of contractions. 4 The COX-1 inhibitor, valeryl salicylate (VSA) (5 ± 100 mM for 60 min), had no eect on either the amplitude or frequency of contractions in the guinea-pig upper urinary tract. In contrast, VSA increased the force of contractions in the proximal and distal renal pelvis of the rat, whilst having little eect on the frequency of contractions. 5 The COX-2 inhibitor, NS-398 (10 ± 100 nM for 60 min) reduced the MI in the guinea-pig upper urinary tract in a concentration-dependent manner. The MIs calculated for the proximal renal pelvis, distal renal pelvis and ureter, were decreased by 72, 64 and 72% respectively, in 100 nM NS-398. NS-398 (10 ± 100 nM) had no eect on any of the three parameters measured in either the proximal or distal renal pelvis of the rat. 6 These data suggest that endogenously-released prostaglandins (PGs) maintain the myogenic contractility of the upper urinary tract in both the guinea-pig and rat. Moreover COX-2 is the primary enzyme involved in synthesizing PGs in the guinea-pig upper urinary tract, while COX-1 appears to be the predominantly active enzyme in the rat.

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