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.

Specimens from the proximal and distal parts of saphenous vein of 16 patients undergoing stripping operations for varicose veins were investigated with pharmacological technique and electron microscopy. The ultrastructural investigation showed a venous wall with increased connective tissue elements such as collagen fibres. In parts endothelial damage could be observed. These changes were about equally frequent in specimens from the proximal and distal great saphenous vein. The pharmacological study showed reduced maximal contraction of varicose veins compared to controls. Moreover there was a slightly higher maximal tension (contraction per unit trans-sectional area) in specimens from the lower leg, compared to the thigh. This means that there is functional disturbance of the smooth muscle function in varicose veins, and other structural elements show significant alterations such as connective tissue and endothelial cells.

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.

The role of the endothelium in the vasomotor control of veins was investigated in 14 isolated ring preparations of presumably normal saphenous veins obtained from vein grafts in connection with vascular surgery. The investigations were performed with the specimens mounted for recording isometric tension in organ baths. Paired rings were used, one normal and the other de-endothelialized by gentle rubbing. The responses to noradrenaline (10(-8)-2 X 10(-5) M), acetylcholine (10(-6) M) and 120 mM KCl solution were tested. After precontraction with 10(-7) M noradrenaline, acetylcholine at 10(-6) M did not induce cholinergic relaxation, but in the majority of experiments induced a further increase in tone. Maximal contraction with noradrenaline was significantly higher in normal compared to de-endothelialized vessels. Therefore, endothelium-derived relaxation as in arteries did not occur in human saphenous veins and the existence of an endothelial-derived contracting factor in response to acetylcholine and noradrenaline is a possibility.

Electron microscopy was performed on normal human ureteral rings before and after incubation in human urine for 30 minutes. A large number of mast cells was detected subepithelially and in close proximity to smooth muscle fibres. Treatment with urine (346 mOsm/l) induced various degrees of degranulation in the majority of mast cells. Some membrane bound granules were found free in the surrounding connective tissue and near smooth muscle cells indicating rupture of the cell membrane. In the functional study frequency and amplitude of peristaltic contractions were studied in-vitro. Addition of urine increased frequency and amplitude of peristaltic contractions and addition of the histamine-1-blocker mepyramine (10(-6) M) partially reversed these changes. It can be concluded that in a situation with urothelial damage such as ureteral calculus, urine can penetrate subepithelially and induce degranulation of mast cells with release of mediators. This is followed by forceful peristaltic contractions which are induced by histamine and other newly formed mediators such as prostaglandins. The process is likely to occur in renal colic with impacted kidney stones.