The pattern of spontaneous rhythmic contractions was studied in isolated preparations from calyx, pelvic, middle and distal parts of the sheep ureter. The frequency of contractions was highest in intrarenal specimens (13.3 +/- 0.8 contractions min-I). The regional difference in contractions is consistent with proximal dominant pacemaker cells. In isolated rings, indomethacin (10(-5) M) inhibited and finally stopped rhythmic motility. After stoppage prostaglandin PGF2 alpha (10(-6)-10(-5) M) promptly re-established contractions in a manner characteristic of each specimen, apparently according to the pre-existent dominant pacemaker (frequency and pattern). This was demonstrated in a frequency analysis which showed a highly significant correlation of pacemaker frequencies before and after indomethacin. Experiments using dual recordings from both ends of a longitudinal preparation (tandem mode) showed that co-ordinated contractile waves travelling from one end to the other could be initiated with PGF2 alpha. These results have been interpreted to indicate that prostaglandins in ureteral smooth muscle play a predominant role in co-ordinating intercellular impulse transmission for which gap junctions could be responsible. The presence of such structures, as clearly demonstrated by an ultrastructural study, lends support to this hypothesis.

Ureteral motility was studied in isolated preparations obtained from 19 patients at surgery. Contraction was monitored in an organ bath and contraction recorded isometrically. In all but one patient rhythmic activity with a frequency of 2.0 +/- 0.3 contractions/min was recorded. In 6 patients contractions had to be elicited by stimulation with prostaglandin E2 or F2 alpha. In the remaining cases motility started spontaneously within 30 min. In patients with bilharzia nephropathy various pathological types of contraction were recorded. Motility was dose-dependently inhibited with indomethacin.

To determine the effect of prostaglandin-synthesis inhibition on ureteral motility, isolated rings of sheep ureters were suspended for recording isometric tension in organ baths filled with Krebs-Henseleit solution. The non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac sodium (10(-5) M) inhibited rhythmic ureteral motility by reducing frequency, amplitude and finally stopping contractions. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and thromboxane B2 were determined by radioimmunoassay in the bathing solution before and after addition of NSAIDs. Peak contractile activity at 100 min of suspension was associated with increased concentration of all three prostanoids and 50 min after addition of indomethacin and diclofenac sodium when rhythmic contractions stopped, concentration dropped to low levels. The concentration of prostaglandins released into the organ bath were not quantitatively related to the frequency of contractions and therefore do not seem to affect pacemaker activity within ureteral smooth muscle but rather intercellular recruitment of myo-genically active fibres. These findings indicate that prostaglandins play a role in the motor control of the ureter, and that non-steroidal anti-inflammatory drugs exert an inhibitory action.

The objective of this study was to evaluate the effect of two non-steroid anti-inflammatory drugs, indomethacin and metamizole, on ureteral peristalsis during acute occlusion similar to the situation in renal colic. In 12 pentobarbital anesthetized sheep, both ureters were cannulated and the frequency of ureteral contractions, urine flow, mean ureteral pressure and blood pressure were recorded during 10-min control and i.v. drug administration periods. Both indomethacin (1-2 mg/kg) and metamizole (60-120 mg/kg) showed a dose dependent reduction in peristaltic frequency without reduction of the mean pressure. In addition, the pressure amplitude of the peristaltic waves was also lowered, particularly with indomethacin. Only indomethacin reduced the urine flow. Arterial blood pressure was elevated by both drugs, particularly after the first dose of indomethacin. It can be concluded that indomethacin and metamizole reduce ureteral peristaltic frequency, probably blocking the impulse transmission at the ureteropelvic junction.

In this study of normal adult human and ovine ureters, a characteristic distribution of a large population of typical mast cells was described by light and electron microscopy. Pharmacological studies were used to ascribe a functional role for these cells in normal and pathological states. In the structural investigations typical mast cells with their cytoplasm packed with characteristic electron dense granules were found in close vicinity to smooth muscle cells. A close association between mast cells and a fibroblast like La-cell and non myelinated nerve fibers was noted. The prevalence of mast cells was higher in human ureters. Human and sheep ureteral ring preparations exhibited spontaneous rhythmical contractions in vitro. Addition of histamine (10(-6)-10(-5) M) induced an increase in the frequency of contractions and enhanced the basal tone particularly in human samples. It is likely that histamine under pathological conditions such as renal colic and inflammatory reactions is released from mast cells within the ureter and induces a state of forceful contractions and pain fibre stimulation.