Endothelin-1-induced activation of rat renal pelvic contractions depends on cyclooxygenase-1 and Rho kinase

Upper urinary tract peristalsis is generated in the proximal renal pelvis that connects to the renal parenchyma at the pelvis-kidney junction. It may be exposed to the high renal endothelin-1 (ET-1) concentrations. Dietary NaCl restriction increases renal pelvic ETA receptor expression. We investigated the contribution of ETA and ETB receptors to ET-1-stimulated rat renal pelvic contractions and whether the sensitivity of renal pelvic contractile activity to ET-1 stimulation increases with dietary NaCl restriction. We tested whether ET-1-induced contractile activity depends on cyclooxygenase (COX)-1 or -2 and to what extent spontaneous as well as agonist-induced peristalsis depends on Rho kinases (ROCK). Contractions of isolated renal pelvises were investigated by myography. ET-1 concentration-dependently increased pelvic contractile activity up to 400% of basal activity. ETA but not ETB receptor blockade inhibited ET-1-induced pelvic contractions. Basal and ET-1-stimulated contractions were similar in renal pelvises from rats on a high-NaCl diet or on a NaCl-deficient diet. COX-1 inhibition reduced spontaneous and almost completely blocked the ET-1-induced pelvic contractions. ROCK inhibition reduced spontaneous and ET-1 stimulated pelvic contractile activity by 90%. RT-PCR revealed that both ROCK isoenzymes are present in the renal pelvic wall. Western blot analyses did not show increased phosphorylation of ROCK substrates myosin phosphatase target subunit 1, ezrin, radixin, and moesin in ET-1-treated isolated renal pelvises. ET-1 is a powerful ETA receptor-dependent activator of renal pelvic contractions. COX-1 and ROCK activity are required for the ET-1 effects on pelvic contractions, which are not significantly affected by dietary NaCl intake.

Effect of peristaltic contractions of the renal pelvic wall on solute concentrations of the renal inner medulla in the hamster

The mechanism of solute accumulation in the renal inner medulla remains an unresolved issue. Experiments were carried out in hamsters to address the possibility that the peristaltic contractions of the renal pelvic wall surrounding the inner medulla play a role in the inner medullary concentrating process. The right renal pelvis was subjected to one of four manipulations (surgical removal of the pelvic wall, paralysis of the pelvic wall with xylocaine, inhibition of pelvic contractions by direct application of heat, or sham treatment) followed by analysis of the inner medullary solute concentrations in the right kidney vs. the untouched left kidney. Removal of the pelvic wall resulted in a marked reduction in inner medullary osmolality, confirming prior observations. Paralysis of the pelvic wall with xylocaine produced a similar decrease in inner medullary osmolality, despite the fact that urine flow was maintained. In contrast, sham treatment (surgical exposure of the right renal pelvic wall without any further manipulation) did not decrease inner medullary osmolality. To test whether the decrease in urinary osmolality following xylocaine treatment could have been due to a side effect of the drug, pelvic peristaltic contractions were eliminated in another way, by direct application of heat to denature the smooth muscle of the pelvic wall. This procedure also significantly decreased inner medullary osmolality. We conclude that elimination of the contractions of the renal pelvic wall in the hamster significantly impairs inner medullary concentrating ability.

Regulation of renal pelvic pressure by diuresis and micturition

The influence of the voiding cycle and diuresis on the hydrodynamic pressures of the renal pelvis in the multicalyceal kidney of miniature pigs has been examined. Identification of the pressure patterns characteristic of the renal pelvis with an undisturbed pelviureteric and ureterovesical junction was emphasized. The frequency and amplitude of contractions in the renal pelvis were measured bilaterally. The patterns of renal pelvic pressure changes were interpreted during bladder filling and emptying and diuresis to evaluate the mechanisms facilitating the pressure isolation of the upper urinary tract. These studies were undertaken in the awake pig equipped with a long-term radiotelemetry implant transmitting renal pelvic and urinary bladder pressure. The results show that renal pelvic contractions are low-pressure events having an amplitude of 10.3 +/- 4.2 cmH2O and a frequency of 6.6 +/- 0.7 contractions/min. During basal hydration, the process of renal pelvic filling and emptying is active, with rhythmic pelvic contractions. The left and right renal pelvis demonstrate approximately equal frequency, 1.04:1.00, but are not synchronous. Furosemide-stimulated diuresis produces radical changes in the renal pelvis by transforming emptying from an active to passive mode and facilitating the transmission of voiding pressures and spontaneous bladder pressures to the kidney.

Renal calyceal and pelvic contraction rhythms

An experimental study of the porcine multicalyceal pacemaker system was undertaken. In particular, the characteristic rhythmicities of in situ calyces were examined as well as rhythmicities between the calyceal system and the renal pelvis using pig kidneys perfused ex vivo via the renal artery. The temporal and spatial organization of calyceal and renal pelvic contraction rates were evaluated by simultaneously recording pressure from the renal pelvis and from three calyces. The results obtained from 15 kidneys indicate that the upper, middle, and lower calyces contract rhythmically at the essentially equal rates of 12.8 +/- 2.4, 14.0 +/- 1.6, and 13.06 +/- 2.3 min-1. The interaction between the activities of different calyces was analyzed by measuring the phase of individual calyceal contractions. Phase locking, coordination of contraction and phase oscillation, systematic fluctuations, or divergence of phase were obtained in most preparations, indicating the existance of a mechanism of coherent intercalyceal coupling. During periods in which phase locking occurred, pelvic contractions were related to all of the observed calyceal regions. When phase oscillation was present, the region of calyceal system evidencing a higher frequency was associated with pelvic contraction, whereas in the absence of calyceal coupling renal pelvic contractions could not be correlated to calyceal activity.

Pyeloureteral dynamics in the intact and chronically obstructed multicalyceal kidney

The transport of urine in the upper urinary tract of the multicalyceal kidney was studied in healthy and chronically obstructed pigs in terms of renal pelvic pressure, rate of and coordination of ureteral contractions, and bolus volume. The variations of these parameters to diuresis was examined by incremental elevation of urine output effected by intravenous infusion of mannitol. In 16 healthy animals the mean variation in urine flow was 0.01-3.20 ml/min, the change in peristaltic rate ranged from 0.763 to 5.125 min-1, and bolus volume from 0.003 to 2.083 ml.. In 14 chronically obstructed kidneys, for a mean variation in urine flow of 0.006-5.4 ml/min, peristaltic rate ranged from 0.237 to 6.095 min-1 and bolus volume from 0.00 to 1.80 ml. Discoordinated contractions, bursts of peristalsis, and incompletely transmitted pelvic contractions were characteristic of a chronically obstructed system. These observations are compared with the unobstructed unicalyceal and multicalyceal kidney. The disrupting impact of chronic ureteral obstruction on the hierarchical organization of the pyeloureteral pacemaker system is discussed.