Effects of selective inhibitors of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) on the spontaneous myogenic contractions in the upper urinary tract of the guinea-pig and rat.

Abstract

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. The guinea-pig upper urinary tract contracted at a frequency (7.52+/-0.3 min(-1) at 35 degrees C) significantly lower than the frequency in the proximal renal pelvis (21.6+/-1.3 min(-1)) and in the distal renal pelvis and ureter (20.2+/-1.4 min(-1)) of the rat (at 30 degrees C). Indomethacin (>/=1 microM for 60 min), decreased the motility index (amplitudexfrequency) (MI) in all three regions of the guinea-pig upper urinary tract, an effect which mainly arose from a decrease in the frequency of contractions. In the rat, indomethacin (1 - 30 microM for 60 min) significantly decreased the MI calculated in the proximal renal pelvis (>/=30 microM indomethacin), and in the distal renal pelvis (>/=10 microM indomethacin), arising from a significant decrease in the amplitude of contractions. The COX-1 inhibitor, valeryl salicylate (VSA) (5 - 100 microM for 60 min), had no effect 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 effect on the frequency of contractions. 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 effect on any of the three parameters measured in either the proximal or distal renal pelvis of the rat. 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.